Proteopedia - User contributions [en]

User:Marvin O'Neal/Antibody OspA and OspB

2012-05-04T19:22:02Z

Safa Abdelhakim:

==Introduction==
===''Borrelia burgdoferi''===

The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/ Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to certain forms of complement-dependent immune response by the evasion of the [http://en.wikipedia.org/wiki/Alternative_complement_pathway alternative complement pathway] and the blocking of complement [http://en.wikipedia.org/wiki/Complement_component_3 C3].<ref>PMID:18080415</ref> This resistance increases the importance of the complement independent immune response when combating ''B. burgdorferi''. Certain fragment antigen binding regions ([http://en.wikipedia.org/wiki/Fragment_antigen-binding fab]) of IgG and IgM monoclonal antibodies (mAbs) are bactericidal even in the absence of complement. Binding of these fabs to their corresponding outer surface protein (OspA and OspB) of ''B. burgdoferi'' leads to the lysis of the bacteria.<ref>PMID:15864264</ref>

===Fragment Antigen Binding (fab)===
[[Image:Fab reigon.png|right|thumb|Digestion of an antibody by Papain separates the fab reigons from the antibody]]
Fab consists of a [http://en.wikipedia.org/wiki/Immunoglobulin_heavy_chain heavy chain] and [http://en.wikipedia.org/wiki/Immunoglobulin_light_chain light chain] and each chain is composed of a variable and a constant region. The [http://en.wikipedia.org/wiki/Paratope paratope] is located in the N terminal of the variable region of the heavy and light chains of the fab. H6831 and CB2 are IgG mAbs that targets the C-terminal of OspB and LA-2 is an IgM mAb that targets the C-terminal of OspA.<ref>PMID:107164</ref>

==OspB and H6831==
<table width='500' align='right' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><Structure load='1RJL' size='400' frame='true' align='center' scene='Studio:G1SecL01/1/10' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''OspB-H6831 Complex''' (<scene name='Studio:G1SecL01/1/10'>Initial Scene</scene>)<br>
<scene name='Studio:G1SecL01/1/11'>OspB</scene>''':''' <scene name='Studio:G1SecL01/1/31'>Loop 1</scene> <scene name='Studio:G1SecL01/1/32'>(w/ His 52)</scene> ·· <scene name='Studio:G1SecL01/1/33'>Loop 2</scene> ·· <scene name='Studio:G1SecL01/1/34'>Lysine 253</scene> <scene name='Studio:G1SecL01/1/35'>(CPK coloring)</scene> ·· <scene name='Studio:G1SecL01/1/36'>Loop 3</scene> <br>
<scene name='Studio:G1SecL01/1/12'>H6831</scene>''': '''
<scene name='Studio:G1SecL01/1/14'>Heavy Chain</scene> ·· <scene name='Studio:G1SecL01/1/13'>Light Chain</scene> ·· <scene name='Studio:G1SecL01/1/37'>Tyr-Trp-Glu-His</scene> <br> <scene name='Studio:G1SecL01/1/30'>OspB-H6831 Complex</scene>''': ''' <scene name='Studio:G1SecL01/1/38'>Residues 218-220</scene><br>
<scene name='Studio:G1SecL01/3/2'> OspB Unbound </scene> ''':''' <scene name='Studio:G1SecL01/3/3'> Central β Sheet Strands 1-4 </scene>

</center></td></tr></table>

===Interaction between OspB and H6831===
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

The <scene name='Studio:G1SecL01/1/30'>OspB-H6831 complex</scene> consist of two components, the outer surface protein <scene name='Studio:G1SecL01/1/11'>OspB</scene> and the <scene name='Studio:G1SecL01/1/12'>fab</scene>, which is subdivided into the <scene name='Studio:G1SecL01/1/14'>heavy chain</scene> and the <scene name='Studio:G1SecL01/1/13'>light chain</scene>. Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the <scene name='Studio:G1SecL01/1/15'>three adjacent surface-exposed loops</scene> at the C-terminal of OspB and some <scene name='Studio:G1SecL01/1/37'>residues on the fab heavy chain</scene> that include tyrosine, tryptophan, glutamate, and histidine.<ref name=becker>PMID:15713683</ref>

The majority of hydrogen bonds and electrostatic interactions are between <scene name='Studio:G1SecL01/1/33'>Loop2</scene> (residues 250-254) and the fab heavy chain. <scene name='Studio:G1SecL01/1/34'>Lys 253</scene> in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 interacts with the two aromatic residues on the fab heavy chain, tyrosine and tryptophan. It also makes hydrogen bonds with the glutamate 50 in the heavy chain of the fab and forms an ionic bond. Carbonyl in <scene name='Studio:G1SecL01/1/31'>loop 1</scene> of the OspB interacts with <scene name='Studio:G1SecL01/1/32'>histidine 52</scene> in the fab heavy chain. <scene name='Studio:G1SecL01/1/36'>Loop 3</scene> of OspB interacts with fab light chain.<ref name=becker />

===Structural changes to OspB in the complexed form===
The binding of H6831 to OspB leads to some conformational changes in OspB compared to its <scene name='Studio:G1SecL01/3/2'> unbound form </scene>. [http://en.wikipedia.org/wiki/Crystallography Crystallography] has shown that the most significant difference is the loss of the <scene name='Studio:G1SecL01/3/3'>central β sheet strands 1-4 </scene>.<ref name=becker /> The loss of these β sheets may be due to conformational change as a result of the binding or a disorder that could have occurred during a crystallization of the complex. Both small positional shifts near the fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the fab-binding site <scene name='Studio:G1SecL01/1/38'>at residues 218-220</scene>. In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap the position of the missing sheet.

===Bactericidal action===
The fab binding destabilizes the [http://en.wikipedia.org/wiki/Bacterial_outer_membrane outer membrane] (OM) of B. burdorferi, with subsequent formation of [http://en.wikipedia.org/wiki/Spheroplast spheroplasts]. It has been observed that the bactericidal action, but not the binding, requires the presence of divalent cations (Mg<sup>2+</sup> and Ca<sup>2+</sup>), and
fab is unable to clear bacteria in the absence of these cations.<ref name=ding /> It is speculated that OspB-Cb2 (a fab similar to H6831) complexes could lead to the lysis of the cell by creating physical openings in the OM, allowing for rapid infusion of electrolytes and increasing the [http://en.wikipedia.org/wiki/Osmolarity osmolarity] of the [http://en.wikipedia.org/wiki/Periplasm periplasm].<ref>PMID:9125579</ref>

==OspA and LA-2==

<table width='500' align='right' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><Structure load='1FJ1' size='400' frame='true' align='center' scene='Studio:G1SecL01/2/1' />
</td></tr><tr><td bgcolor='#eeeeee'><center>'''OspA-LA2 Complex''' (<scene name='Studio:G1SecL01/2/1'>Initial Scene</scene>)<br>
<scene name='Studio:G1SecL01/2/1'>OspA-LA2 Complex</scene>''':''' <scene name='Studio:G1SecL01/2/2'>Three Loops</scene> '''··''' <scene name='Studio:G1SecL01/2/3'>Ser 206</scene>
</center></td></tr></table>

===OspA===
<scene name='Studio:G1SecL01/2/1'>Restore Original Scene</scene>

OspA is usually undetectable in the early stages of Lyme disease, and is down regulated when OspC is expressed.<ref name=ospc>PMID:11230121</ref> OspA is 53% similar to OspB. Despite their similarity, OspB is susceptible to cleavage by exogenous [http://en.wikipedia.org/wiki/Protease proteases] both ''in vivo'' and ''in vitro'', whereas OspA is relatively resistant in both cases.<ref name=becker />

===Interaction between OspA and LA-2===
LA-2 is an IgM murine monoclonal antibody that interacts with <scene name='Studio:G1SecL01/2/2'> three exposed loops </scene> on the C-terminal of OspA. These interactions include eight direct [[hydrogen bonds]], four solvent-bridged hydrogen bonds, three ion pairs, and numerous van der Waals interactions.<ref name=ding />

===Structural changes to OspA in the complexed form===
Conformational changes upon the binding of OspA and LA-2 show that LA-2 recognition of OspA involves an induced fit mechanism where the conformations of loops 1-3 shift to optimize complementarity to the antigen-combining site.<ref name=ding /> The overall structure of the C-terminal of OspA is unchanged upon the binding of LA-2 with comparison to the free OspA. The maximum atomic shift is 4.7Å at the site of <scene name='Studio:G1SecL01/2/3'>Ser 206</scene>.<ref name=ding>PMID: 11183781</ref>

==Medical Application==

''B. burgdoferi'' is able to escape human immune response because the outer surface proteins, to which the immune system responds, are variable. The effectiveness of different Osp molecules as [http://en.wikipedia.org/wiki/Vaccine vaccines] can vary depending on their variability. OspC and OspB are highly polymorphic. Variability of OspC was even observed in strains collected from single geographical areas. <ref name=ospc /> Observed variations of OspB in ''B. burgdoferi'' (including its absence from the bacteria) are not accounted for by major [http://en.wikipedia.org/wiki/Dna DNA] arrangements or failure in [http://en.wikipedia.org/wiki/Transcription_(genetics) transcription] of the OspB gene. This indicates that the OspB gene may code for a variety of proteins, making OspB a poor candidate for use in vaccines.<ref>PMID:2668185</ref> OspA is the most conserved; of the three exposed loops, only loop 1 is variable while loops 2 and 3 are conserved. This makes OspA a more consistent antigen (compared to OspB and OspC) for the immune system to target and usable as a vaccine to Lyme disease.<ref name=ding />

References: {{reflist}}

User:Marvin O'Neal/Antibody OspA and OspB

2012-05-04T19:01:14Z

Safa Abdelhakim:

==Introduction==
===''Borrelia burgdoferi''===

The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/ Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to certain forms of complement-dependent immune response by the evasion of the [http://en.wikipedia.org/wiki/Alternative_complement_pathway alternative complement pathway] and the blocking of complement [http://en.wikipedia.org/wiki/Complement_component_3 C3].<ref>PMID:18080415</ref> This resistance increases the importance of the complement independent immune response when combating ''B. burgdorferi''. Certain fragment antigen binding regions ([http://en.wikipedia.org/wiki/Fragment_antigen-binding fab]) of IgG and IgM monoclonal antibodies (mAbs) are bactericidal even in the absence of complement. Binding of these fabs to their corresponding outer surface protein (OspA and OspB) of ''B. burgdoferi'' leads to the lysis of the bacteria.<ref>PMID:15864264</ref>

===Fragment Antigen Binding (fab)===
[[Image:Fab reigon.png|right|thumb|Digestion of an antibody by Papain separates the fab reigons from the antibody]]
Fab consists of a [http://en.wikipedia.org/wiki/Immunoglobulin_heavy_chain heavy chain] and [http://en.wikipedia.org/wiki/Immunoglobulin_light_chain light chain] and each chain is composed of a variable and a constant region. The [http://en.wikipedia.org/wiki/Paratope paratope] is located in the N terminal of the variable region of the heavy and light chains of the fab. H6831 and CB2 are IgG mAbs that targets the C-terminal of OspB and LA-2 is an IgM mAb that targets the C-terminal of OspA.<ref>PMID:107164</ref>

==OspB and H6831==
<table width='500' align='right' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><Structure load='1RJL' size='400' frame='true' align='center' scene='Studio:G1SecL01/1/10' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''OspB-H6831 Complex''' (<scene name='Studio:G1SecL01/1/10'>Initial Scene</scene>)<br>
<scene name='Studio:G1SecL01/1/11'>OspB</scene>''':''' <scene name='Studio:G1SecL01/1/31'>Loop 1</scene> <scene name='Studio:G1SecL01/1/32'>(w/ His 52)</scene> ·· <scene name='Studio:G1SecL01/1/33'>Loop 2</scene> ·· <scene name='Studio:G1SecL01/1/34'>Lysine 253</scene> <scene name='Studio:G1SecL01/1/35'>(CPK coloring)</scene> ·· <scene name='Studio:G1SecL01/1/36'>Loop 3</scene> <br>
<scene name='Studio:G1SecL01/1/12'>H6831</scene>''': '''
<scene name='Studio:G1SecL01/1/14'>Heavy Chain</scene> ·· <scene name='Studio:G1SecL01/1/13'>Light Chain</scene> ·· <scene name='Studio:G1SecL01/1/37'>Tyr-Trp-Glu-His</scene> <br> <scene name='Studio:G1SecL01/1/30'>OspB-H6831 Complex</scene>''': ''' <scene name='Studio:G1SecL01/1/38'>Residues 218-220</scene><br>
<scene name='Studio:G1SecL01/3/2'> OspB Unbound </scene> ''':''' <scene name='Studio:G1SecL01/3/3'> Central β Sheet Strands 1-4 </scene>

</center></td></tr></table>

===Interaction between OspB and H6831===
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

The <scene name='Studio:G1SecL01/1/30'>OspB-H6831 complex</scene> consist of two components, the outer surface protein <scene name='Studio:G1SecL01/1/11'>OspB</scene> and the <scene name='Studio:G1SecL01/1/12'>fab</scene>, which is subdivided into the <scene name='Studio:G1SecL01/1/14'>heavy chain</scene> and the <scene name='Studio:G1SecL01/1/13'>light chain</scene>. Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the <scene name='Studio:G1SecL01/1/15'>three adjacent surface-exposed loops</scene> at the C-terminal of OspB and some <scene name='Studio:G1SecL01/1/37'>residues on the fab heavy chain</scene> that include tyrosine, tryptophan, glutamate, and histidine.<ref name=becker>PMID:15713683</ref>

The majority of hydrogen bonds and electrostatic interactions are between <scene name='Studio:G1SecL01/1/33'>Loop2</scene> (residues 250-254) and the fab heavy chain. <scene name='Studio:G1SecL01/1/34'>Lys 253</scene> in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 interacts with the two aromatic residues on the fab heavy chain, tyrosine and tryptophan. It also makes hydrogen bonds with the glutamate 50 in the heavy chain of the fab and forms an ionic bond. Carbonyl in <scene name='Studio:G1SecL01/1/31'>loop 1</scene> of the OspB interacts with <scene name='Studio:G1SecL01/1/32'>histidine 52</scene> in the fab heavy chain. <scene name='Studio:G1SecL01/1/36'>Loop 3</scene> of OspB interacts with fab light chain.<ref name=becker />

===Structural changes to OspB in the complexed form===
The binding of H6831 to OspB leads to some conformational changes in OspB compared to its <scene name='Studio:G1SecL01/3/2'> unbound form </scene>. [http://en.wikipedia.org/wiki/Crystallography Crystallography] has shown that the most significant difference is the loss of the <scene name='Studio:G1SecL01/3/3'>central β sheet strands 1-4 </scene>.<ref name=becker /> The loss of these β sheets may be due to conformational change as a result of the binding or a disorder that could have occurred during a crystallization of the complex. Both small positional shifts near the fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the fab-binding site <scene name='Studio:G1SecL01/1/38'>at residues 218-220</scene>. In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap the position of the missing sheet.

===Bactericidal action===
The fab binding destabilizes the [http://en.wikipedia.org/wiki/Bacterial_outer_membrane outer membrane] (OM) of B. burdorferi, with subsequent formation of [http://en.wikipedia.org/wiki/Spheroplast spheroplasts]. It has been observed that the bactericidal action, but not the binding, requires the presence of divalent cations (Mg<sup>2+</sup> and Ca<sup>2+</sup>), and
fab is unable to clear bacteria in the absence of these cations.<ref name=ding /> It is speculated that OspB-Cb2 (a fab similar to H6831) complexes could lead to the lysis of the cell by creating physical openings in the OM, allowing for rapid infusion of electrolytes and increasing the [http://en.wikipedia.org/wiki/Osmolarity osmolarity] of the [http://en.wikipedia.org/wiki/Periplasm periplasm].<ref>PMID:9125579</ref>

==OspA and LA-2==

<table width='500' align='right' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><Structure load='1FJ1' size='400' frame='true' align='center' scene='Studio:G1SecL01/2/1' />
</td></tr><tr><td bgcolor='#eeeeee'><center>'''OspA-LA2 Complex''' (<scene name='Studio:G1SecL01/2/1'>Initial Scene</scene>)<br>
<scene name='Studio:G1SecL01/2/1'>OspA-LA2 Complex</scene>''':''' <scene name='Studio:G1SecL01/2/2'>Three Loops</scene> '''··''' <scene name='Studio:G1SecL01/2/3'>Ser 206</scene>
</center></td></tr></table>

===OspA===
<scene name='Studio:G1SecL01/2/1'>Restore Original Scene</scene>

OspA is usually undetectable in the early stages of Lyme disease, and is down regulated when OspC is expressed.<ref name=ospc>PMID:11230121</ref> OspA is 53% similar to OspB. Despite their similarity, OspB is susceptible to cleavage by exogenous [http://en.wikipedia.org/wiki/Protease proteases] both ''in vivo'' and ''in vitro'', whereas OspA is relatively resistant in both cases.<ref name=becker />

===Interaction between OspA and LA-2===
LA-2 is an IgM murine monoclonal antibody that interacts with <scene name='Studio:G1SecL01/2/2'> three exposed loops </scene> on the C-terminal of OspA. These interactions include eight direct [[hydrogen bonds]], four solvent-bridged hydrogen bonds, three ion pairs, and numerous van der Waals interactions.<ref name=ding />

===Structural changes to OspA in the complexed form===
Conformational changes upon the binding of OspA and LA-2 show that LA-2 recognition of OspA involves an induced fit mechanism where the conformations of loops 1-3 shift to optimize complementarity to the antigen-combining site.<ref name=ding /> The overall structure of the C-terminal of OspA is unchanged upon the binding of LA-2 with comparison to the free OspA. The maximum atomic shift is 4.7Å at the site of <scene name='Studio:G1SecL01/2/3'>Ser 206</scene>.<ref name=ding>PMID: 11183781</ref>

==Medical Application==

''B. burgdoferi'' is able to escape human immune response because the outer surface proteins, to which the immune system responds, are variable, particularly OspB and OspC.<ref name=ospc /> The effectiveness of different Osp molecules as [http://en.wikipedia.org/wiki/Vaccine vaccines] can vary. OspB is highly polymorphic, and observed variations of the protein in ''B. burgdoferi'' (including its absence from the bacteria) are not accounted for by major [http://en.wikipedia.org/wiki/Dna DNA] arrangements or failure in [http://en.wikipedia.org/wiki/Transcription_(genetics) transcription] of the OspB gene. This indicates that the OspB gene may code for a variety of proteins, making OspB a poor candidate for use in vaccines.<ref>PMID:2668185</ref> OspA is the most conserved; of the three exposed loops, only loop 1 is variable while loops 2 and 3 are conserved. This makes OspA a more consistent antigen (compared to OspB and OspC) for the immune system to target and usable as a vaccine to Lyme disease.<ref name=ding />

References: {{reflist}}

User:Marvin O'Neal/Antibody OspA and OspB

2012-05-03T13:45:36Z

Safa Abdelhakim:

==Introduction==
===''Borrelia burgdoferi''===

The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/ Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to certain forms of complement-dependent immune response by the evasion of the [http://en.wikipedia.org/wiki/Alternative_complement_pathway alternative complement pathway] and the blocking of complement [http://en.wikipedia.org/wiki/Complement_component_3 C3].<ref>PMID:18080415</ref> This resistance increases the importance of the complement independent immune response when combating ''B. burgdorferi''. Certain fragment antigen binding regions ([http://en.wikipedia.org/wiki/Fragment_antigen-binding fab]) of IgG and IgM monoclonal antibodies (mAbs) are bactericidal even in the absence of complement. Binding of these fabs to their corresponding outer surface protein (OspA and OspB) of ''B. burgdoferi'' leads to the lysis of the bacteria.<ref>PMID:15864264</ref>

===Fragment Antigen Binding (fab)===
[[Image:Fab reigon.png|right|thumb|Digestion of an antibody by Papain separates the fab reigons from the antibody]]
Fab consists of a [http://en.wikipedia.org/wiki/Immunoglobulin_heavy_chain heavy chain] and [http://en.wikipedia.org/wiki/Immunoglobulin_light_chain light chain] and each chain is composed of a variable and a constant region. The [http://en.wikipedia.org/wiki/Paratope paratope] is located in the N terminal of the variable region of the heavy and light chains of the fab. H6831 and CB2 are IgG mAbs that targets the C-terminal of OspB and LA-2 is an IgM mAb that targets the C-terminal of OspA.<ref>PMID:107164</ref>

==OspB and H6831==
<table width='500' align='right' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><Structure load='1RJL' size='400' frame='true' align='center' scene='Studio:G1SecL01/1/10' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''OspB-H6831 Complex''' (<scene name='Studio:G1SecL01/1/10'>Initial Scene</scene>)<br>
<scene name='Studio:G1SecL01/1/11'>OspB</scene>''':''' <scene name='Studio:G1SecL01/1/25'>Loop 1</scene> <scene name='Studio:G1SecL01/1/29'>(w/ His 52)</scene> ·· <scene name='Studio:G1SecL01/1/24'>Loop2</scene> ·· <scene name='Studio:G1SecL01/1/28'>Lysine 253</scene> <scene name='Studio:G1SecL01/1/27'>(CPK coloring)</scene> ·· <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> <br>
<scene name='Studio:G1SecL01/1/12'>H6831</scene>''': '''
<scene name='Studio:G1SecL01/1/14'>Heavy Chain</scene> ·· <scene name='Studio:G1SecL01/1/13'>Light Chain</scene> ·· <scene name='Studio:G1SecL01/1/16'>Tyr-Trp-Glu-His</scene> <br> <scene name='Studio:G1SecL01/1/22'>OspB-H6831 Complex</scene>''': ''' <scene name='Studio:G1SecL01/1/23'>Residues 218-220</scene><br>
<scene name='Studio:G1SecL01/3/2'> OspB Unbound </scene> ''':''' <scene name='Studio:G1SecL01/3/3'> Central β Sheet Strands 1-4 </scene>

</center></td></tr></table>

===Interaction between OspB and H6831===
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

The <scene name='Studio:G1SecL01/1/22'>OspB-H6831 complex</scene> consist of two components, the outer surface protein <scene name='Studio:G1SecL01/1/11'>OspB</scene> and the <scene name='Studio:G1SecL01/1/12'>fab</scene>, which is subdivided into the <scene name='Studio:G1SecL01/1/14'>heavy chain</scene> and the <scene name='Studio:G1SecL01/1/13'>light chain</scene>. Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the <scene name='Studio:G1SecL01/1/15'>three adjacent surface-exposed loops</scene> at the C-terminal of OspB and some <scene name='Studio:G1SecL01/1/16'>residues on the fab heavy chain</scene> that include tyrosine, tryptophan, glutamate, and histidine.<ref name=becker>PMID:15713683</ref>

The majority of hydrogen bonds and electrostatic interactions are between <scene name='Studio:G1SecL01/1/24'>Loop2</scene> (residues 250-254) and the fab heavy chain. <scene name='Studio:G1SecL01/1/28'>Lys 253</scene> in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 interacts with the two aromatic residues on the fab heavy chain, tyrosine and tryptophan. It also makes hydrogen bonds with the glutamate 50 in the heavy chain of the fab and forms an ionic bond. Carbonyl in <scene name='Studio:G1SecL01/1/25'>loop 1</scene> of the OspB interacts with <scene name='Studio:G1SecL01/1/29'>histidine 52</scene> in the fab heavy chain. <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> of OspB interacts with fab light chain.<ref name=becker />

===Structural changes to OspB in the complexed form===
The binding of H6831 to OspB leads to some conformational changes in OspB compared to its <scene name='Studio:G1SecL01/3/2'> unbound form </scene>. [http://en.wikipedia.org/wiki/Crystallography Crystallography] has shown that the most significant difference is the loss of the <scene name='Studio:G1SecL01/3/3'>central β sheet strands 1-4 </scene>.<ref name=becker /> The loss of these β sheets may be due to conformational change as a result of the binding or a disorder that could have occurred during a crystallization of the complex. Both small positional shifts near the fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the fab-binding site <scene name='Studio:G1SecL01/1/23'>at residues 218-220</scene>. In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap the position of the missing sheet.

===Bactericidal action===
The fab binding destabilizes the [http://en.wikipedia.org/wiki/Bacterial_outer_membrane outer membrane] (OM) of B. burdorferi, with subsequent formation of [http://en.wikipedia.org/wiki/Spheroplast spheroplasts]. It has been observed that the bactericidal action, but not the binding, requires the presence of divalent cations (Mg<sup>2+</sup> and Ca<sup>2+</sup>), and
fab is unable to clear bacteria in the absence of these cations.<ref name=ding /> It is speculated that OspB-Cb2 (a fab similar to H6831) complexes could lead to the lysis of the cell by creating physical openings in the OM, allowing for rapid infusion of electrolytes and increasing the [http://en.wikipedia.org/wiki/Osmolarity osmolarity] of the [http://en.wikipedia.org/wiki/Periplasm periplasm].<ref>PMID:9125579</ref>

==OspA and LA-2==

<table width='500' align='right' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><Structure load='1FJ1' size='400' frame='true' align='center' scene='Studio:G1SecL01/2/1' />
</td></tr><tr><td bgcolor='#eeeeee'><center>'''OspA-LA2 Complex''' (<scene name='Studio:G1SecL01/2/1'>Initial Scene</scene>)<br>
<scene name='Studio:G1SecL01/2/1'>OspA-LA2 Complex</scene>''':''' <scene name='Studio:G1SecL01/2/2'>Three Loops</scene> '''··''' <scene name='Studio:G1SecL01/2/3'>Ser 206</scene>
</center></td></tr></table>

===OspA===
<scene name='Studio:G1SecL01/2/1'>Restore Original Scene</scene>

OspA is usually undetectable in the early stages of Lyme disease, and is down regulated when OspC is expressed.<ref name=ospc>PMID:11230121</ref> OspA is 53% similar to OspB. Despite their similarity, OspB is susceptible to cleavage by exogenous [http://en.wikipedia.org/wiki/Protease proteases] both ''in vivo'' and ''in vitro'', whereas OspA is relatively resistant in both cases.<ref name=becker />

===Interaction between OspA and LA-2===
LA-2 is an IgM murine monoclonal antibody that interacts with <scene name='Studio:G1SecL01/2/2'> three exposed loops </scene> on the C-terminal of OspA. These interactions include eight direct [[hydrogen bonds]], four solvent-bridged hydrogen bonds, three ion pairs, and numerous van der Waals interactions.<ref name=ding />

===Structural changes to OspA in the complexed form===
Conformational changes upon the binding of OspA and LA-2 show that LA-2 recognition of OspA involves an induced fit mechanism where the conformations of loops 1-3 shift to optimize complementarity to the antigen-combining site.<ref name=ding /> The overall structure of the C-terminal of OspA is unchanged upon the binding of LA-2 with comparison to the free OspA. The maximum atomic shift is 4.7Å at the site of <scene name='Studio:G1SecL01/2/3'>Ser 206</scene>.<ref name=ding>PMID: 11183781</ref>

==Medical Application==

''B. burgdoferi'' is able to escape human immune response because antigens to which the immune system responds (the outer surface proteins) are highly variable, particularly OspB and OspC <ref name=ospc />. Osps can be used for developing vaccinations, however, the effectiveness of different Osp molecules (Osp A, B, and C) for this purpose varies. OspB is highly polymorphic, and observed variations of the protein in ''B. burgdoferi'' (including its absence from the bacteria) are not accounted for by major DNA arrangements or failure in transcription of the OspB gene. This means that the OspB gene codes for a wide variety of possible proteins, making OspB a poor candidate for use in vaccines <ref>PMID:2668185</ref>. However OspA is the most conserved Osp in ''B. burgdoferi''. Only loop 1 of the three exposed loops are variable, and loops 2 and 3 are conserved, making a more consistent antigen for the immune system to target and a better vaccine. <ref name=ding />

References: {{reflist}}

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-30T15:32:12Z

Safa Abdelhakim:

==Introduction==
===''Borrelia burgdoferi''===

The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/ Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to certain forms of complement-dependent immune response by the evasion of the [http://en.wikipedia.org/wiki/Alternative_complement_pathway alternative complement pathway] and the blocking of complement [http://en.wikipedia.org/wiki/Complement_component_3 C3]. <ref>PMID:18080415</ref> This resistance increases the importance of the complement independent immune response when combating ''B. burgdorferi''. Certain fragment antigen binding regions ([http://en.wikipedia.org/wiki/Fragment_antigen-binding fab]) of IgG and IgM monoclonal antibodies (mAbs) are bactericidal even in the absence of complement. Binding of these fabs to their corresponding outer surface protein (OspA and OspB) of ''B. burgdoferi'' leads to the lysis of the bacteria.<ref>PMID:15864264</ref>

===Fragment Antigen Binding (fab)===
[[Image:Fab reigon.png|right|thumb|Digestion of an antibody by Papain separates the fab reigons from the antibody]]
Fab consists of a [http://en.wikipedia.org/wiki/Immunoglobulin_heavy_chain heavy chain] and [http://en.wikipedia.org/wiki/Immunoglobulin_light_chain light chain] and each chain is composed of a variable and a constant region. The [http://en.wikipedia.org/wiki/Paratope paratope] is located in the N terminal of the variable region of the heavy and light chains of the fab. H6831 and CB2 are IgG mAbs that targets the C-terminal of OspB and LA-2 is an IgM mAb that targets the C-terminal of OspA. <ref>PMID:107164</ref>

==OspB and H6831==
<table width='500' align='right' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><Structure load='1RJL' size='400' frame='true' align='center' scene='Studio:G1SecL01/1/10' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''OspB-H6831 Complex''' (<scene name='Studio:G1SecL01/1/10'>Initial Scene</scene>)<br>
<scene name='Studio:G1SecL01/1/11'>OspB</scene>''':''' <scene name='Studio:G1SecL01/1/15'>Three Loops</scene> ·· <scene name='Studio:G1SecL01/1/25'>Loop 1</scene> ·· <scene name='Studio:G1SecL01/1/24'>Loop2</scene> ·· <scene name='Studio:G1SecL01/1/17'>Lysine 253</scene> ·· <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> <br>
<scene name='Studio:G1SecL01/1/12'>H6831</scene>''': '''
<scene name='Studio:G1SecL01/1/14'>Heavy Chain</scene> ·· <scene name='Studio:G1SecL01/1/13'>Light Chain</scene> ·· <scene name='Studio:G1SecL01/1/16'>Tyr-Trp-Glu-His</scene> <br> <scene name='Studio:G1SecL01/1/22'>OspB-H6831 Complex</scene> ''': ''' <scene name='Studio:G1SecL01/1/26'>Beta Sheet Strands 1-4</scene> ·· <scene name='Studio:G1SecL01/1/23'>Residues 218-220</scene>

</center></td></tr></table>

===Interaction between OspB and H6831===
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

The <scene name='Studio:G1SecL01/1/22'>OspB-H6831 complex</scene> consist of two components, the outer surface protein <scene name='Studio:G1SecL01/1/11'>OspB</scene> and the <scene name='Studio:G1SecL01/1/12'>fab</scene>, which is subdivided into the <scene name='Studio:G1SecL01/1/14'>heavy chain</scene> and the <scene name='Studio:G1SecL01/1/13'>light chain</scene>. Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the <scene name='Studio:G1SecL01/1/15'>three adjacent surface-exposed loops</scene> at the C-terminal of OspB and some <scene name='Studio:G1SecL01/1/16'>residues on the fab heavy chain</scene> that include tyrosine, tryptophan, glutamate, and histidine. <ref name=becker>PMID:15713683</ref>

The majority of hydrogen bonds and electrostatic interactions are between <scene name='Studio:G1SecL01/1/24'>Loop2</scene> (residues 250-254) and the fab heavy chain. <scene name='Studio:G1SecL01/1/17'>Lysine 253</scene> in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine and tryptophan. It also makes hydrogen bonds with the glutamate in the heavy chain of the fab and forms an ionic bond. Carbonyl in <scene name='Studio:G1SecL01/1/25'>loop 1</scene> of the OspB interacts with histidine in the fab heavy chain. <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> of OspB interacts with fab light chain. <ref name=becker />
===Structural changes to OspB in the complexed form===
The binding of H6831 to OspB leads to some conformational changes in OspB compared to its free form. Study, done by becker using crystallography, has showed that the most significant difference is the loss of the central <scene name='Studio:G1SecL01/1/26'>beta sheet</scene>, strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the Fab-binding site <scene name='Studio:G1SecL01/1/23'> at residues 218–220</scene>. In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts. <ref name=becker />

===Bactericidal action===
The fab binding destabilizes the [http://en.wikipedia.org/wiki/Bacterial_outer_membrane outer membrane] (OM) of B. burdorferi, with subsequent formation of [http://en.wikipedia.org/wiki/Spheroplast spheroplasts]. It has been observed that the bactericidal action, but not the binding, requires the presence of divalent cations (Mg<sup>2+</sup> and Ca<sup>2+</sup>). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the divalent cations. It was speculated that OspB-Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm, and leading to the lysis of the cell.<ref>PMID:9125579</ref>

==OspA and LA-2==
<Structure load='1FJ1' size='400' frame='true' align='right' caption='OspA-LA2 Complex' scene='Studio:G1SecL01/2/1' />
===OspA===
<scene name='Studio:G1SecL01/2/1'>Restore Original Scene</scene>
OspA is 53% similar to OspB. OspA is usually undetectable in the early stages of lyme disease, because it is down regulated when OspC is expressed (provide citation). Despite the similarity between OspA and OspB, both in vivo and vitro OspB is susceptible to cleavage by exogenous [http://en.wikipedia.org/wiki/Protease proteases], whereas OspA is relatively resistant (Becker, structural). This characteristic might have contributed to OspA being a proper vaccine to lyme disease that is used to prevent transmission of B.burgodorferi from tick vector to mammalian host by complement-independent killing.<ref name=ding />

===Interaction between OspA and LA-2===
LA-2 is an IgM murine monoclonal antibody that interacts with three exposed loop on the C-terminal of OspA. These interactions include eight direct hydrogen bonds, four solvent-bridged hydrogen bonds, three ion pairs, and numerous van der Waals interactions <ref name=ding />.

===Structural changes to OspA in the complexed form===
Conformational changes upon the binding of OspA and LA-2 show that LA-2 recognition of OspA involves an induced fit mechanism where loops 1-3 conformations shift to optimize complementarity to the antigen-combining site <ref name=ding />. The overall structure of the C-terminal of OspA is unchanged upon the binding of LA-2 with comparison to the free OspA. The maximum atomic shift is 4.7Å at the site of Ser206.<ref name=ding>PMID: 11183781</ref>

References: {{reflist}}

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-30T15:22:11Z

Safa Abdelhakim:

==Introduction==
===''Borrelia burgdoferi''===

The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/ Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to certain forms of complement-dependent immune response by the evasion of the [http://en.wikipedia.org/wiki/Alternative_complement_pathway alternative complement pathway] and the blocking of complement [http://en.wikipedia.org/wiki/Complement_component_3 C3]. <ref>PMID:18080415</ref> This resistance increases the importance of the complement independent immune response when combating ''B. burgdorferi''. Certain fragment antigen binding regions ([http://en.wikipedia.org/wiki/Fragment_antigen-binding fab]) of IgG and IgM monoclonal antibodies (mAbs)are bactericidal even in the absence of complement. Binding of these fabs to their corresponding outer surface protein (OspA and OspB) of ''B. burgdoferi'' leads to the lysis of the bacteria.<ref>PMID:15864264</ref>

===Fragment Antigen Binding (fab)===
[[Image:Fab reigon.png|right|thumb|Digestion of an antibody by Papain separates the fab reigons from the antibody]]
Fab consists of a [http://en.wikipedia.org/wiki/Immunoglobulin_heavy_chain heavy chain] and [http://en.wikipedia.org/wiki/Immunoglobulin_light_chain light chain] and each chain is composed of a variable and a constant region. The [http://en.wikipedia.org/wiki/Paratope paratope] is located in the N terminal of the variable region of the heavy and light chains of the fab. H6831 and CB2 are IgG mAbs that targets the C-terminal of OspB and LA-2 is an IgM mAb that targets the C-terminal of OspA. <ref>PMID:107164</ref>

==OspB and H6831==
<table width='500' align='right' cellpadding='5'><tr><td rowspan='2'> </td><td bgcolor='#eeeeee'><Structure load='1RJL' size='400' frame='true' align='center' scene='Studio:G1SecL01/1/10' /></td></tr><tr><td bgcolor='#eeeeee'><center>'''OspB-H6831 Complex''' (<scene name='Studio:G1SecL01/1/10'>Initial Scene</scene>)<br>
<scene name='Studio:G1SecL01/1/11'>OspB</scene>''':''' <scene name='Studio:G1SecL01/1/15'>Three Loops</scene> ·· <scene name='Studio:G1SecL01/1/25'>Loop 1</scene> ·· <scene name='Studio:G1SecL01/1/24'>Loop2</scene> ·· <scene name='Studio:G1SecL01/1/17'>Lysine 253</scene> ·· <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> <br>
<scene name='Studio:G1SecL01/1/12'>H6831</scene>''': '''
<scene name='Studio:G1SecL01/1/14'>Heavy Chain</scene> ·· <scene name='Studio:G1SecL01/1/13'>Light Chain</scene> ·· <scene name='Studio:G1SecL01/1/16'>Tyr-Trp-Glu-His</scene> <br> <scene name='Studio:G1SecL01/1/22'>OspB-H6831 Complex</scene> ''': ''' <scene name='Studio:G1SecL01/1/19'>Beta Sheet Strands 1-4</scene> ·· <scene name='Studio:G1SecL01/1/23'>Residues 218-220</scene>

</center></td></tr></table>

===Interaction between OspB and H6831===
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

The <scene name='Studio:G1SecL01/1/22'>OspB-H6831 complex</scene> consist of two components, the outer surface protein <scene name='Studio:G1SecL01/1/11'>OspB</scene> and the <scene name='Studio:G1SecL01/1/12'>fab</scene>, which is subdivided into the <scene name='Studio:G1SecL01/1/14'>heavy chain</scene> and the <scene name='Studio:G1SecL01/1/13'>light chain</scene>. Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the <scene name='Studio:G1SecL01/1/15'>three adjacent surface-exposed loops</scene> at the C-terminal of OspB and some <scene name='Studio:G1SecL01/1/16'>residues on the fab heavy chain</scene> that include tyrosine, tryptophan, glutamate, and histidine. <ref name=becker>PMID:15713683</ref>

The majority of hydrogen bonds and electrostatic interactions are between <scene name='Studio:G1SecL01/1/24'>Loop2</scene> (residues 250-254) and the fab heavy chain. <scene name='Studio:G1SecL01/1/17'>Lysine 253</scene> in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine and tryptophan. It also makes hydrogen bonds with the glutamate in the heavy chain of the fab and forms an ionic bond. Carbonyl in <scene name='Studio:G1SecL01/1/25'>loop 1</scene> of the OspB interacts with histidine in the fab heavy chain. <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> of OspB interacts with fab light chain. <ref name=becker />
===Structural changes to OspB in the complexed form===
The binding of H6831 to OspB leads to some conformational changes in OspB compared to its free form. Study, done by becker using crystallography, has showed that the most significant difference is the loss of the central <scene name='Studio:G1SecL01/1/19'>beta sheet</scene>, strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a <scene name='Studio:G1SecL01/1/23'>loop opposite the Fab-binding site</scene> at residues 218 –220. In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts. <ref name=becker />

===Bactericidal action===
The fab binding destabilizes the [http://en.wikipedia.org/wiki/Bacterial_outer_membrane outer membrane] (OM) of B. burdorferi, with subsequent formation of [http://en.wikipedia.org/wiki/Spheroplast spheroplasts]. It has been observed that the bactericidal action, but not the binding, requires the presence of divalent cations (Mg<sup>2+</sup> and Ca<sup>2+</sup>). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the divalent cations. It was speculated that OspB-Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm, and leading to the lysis of the cell.<ref>PMID:9125579</ref>

==OspA and LA-2==
<Structure load='1FJ1' size='400' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

===OspA===
OspA is 53% similar to OspB. OspA is usually undetectable in the early stages of lyme disease, because it is down regulated when OspC is expressed (provide citation). Despite the similarity between OspA and OspB, both in vivo and vitro OspB is susceptible to cleavage by exogenous [http://en.wikipedia.org/wiki/Protease proteases], whereas OspA is relatively resistant (Becker, structural). This characteristic might have contributed to OspA being a proper vaccine to lyme disease that is used to prevent transmission of B.burgodorferi from tick vector to mammalian host by complement-independent killing.<ref name=ding />

===Interaction between OspA and LA-2===
LA-2 is an IgM murine monoclonal antibody that interacts with three exposed loop on the C-terminal of OspA. These interactions include eight direct hydrogen bonds, four solvent-bridged hydrogen bonds, three ion pairs, and numerous van der Waals interactions <ref name=ding />.

===Structural changes to OspA in the complexed form===
Conformational changes upon the binding of OspA and LA-2 show that LA-2 recognition of OspA involves an induced fit mechanism where loops 1-3 conformations shift to optimize complementarity to the antigen-combining site <ref name=ding />. The overall structure of the C-terminal of OspA is unchanged upon the binding of LA-2 with comparison to the free OspA. The maximum atomic shift is 4.7Å at the site of Ser206.<ref name=ding>PMID: 11183781</ref>

References: {{reflist}}

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-30T03:05:03Z

Safa Abdelhakim:

==Introduction==
===''Borrelia burgdoferi''===

The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/ Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to certain forms of complement-dependent immune response by the evasion of the [http://en.wikipedia.org/wiki/Alternative_complement_pathway alternative complement pathway] and the blocking of complement [http://en.wikipedia.org/wiki/Complement_component_3 C3]. <ref>PMID:18080415</ref> This resistance increases the importance of the complement independent immune response when combating ''B. burgdorferi''. Certain fragment antigen binding regions ([http://en.wikipedia.org/wiki/Fragment_antigen-binding fab]) of IgG and IgM monoclonal antibodies (mAbs)are bactericidal even in the absence of complement. Binding of these fabs to their corresponding outer surface protein (OspA and OspB) of ''B. burgdoferi'' leads to the lysis of the bacteria.<ref>PMID:15864264</ref>

===Fragment Antigen Binding (fab)===
[[Image:Fab reigon.png|right|thumb|Digestion of an antibody by Papain separates the fab reigons from the antibody]]
Fab consists of a [http://en.wikipedia.org/wiki/Immunoglobulin_heavy_chain heavy chain] and [http://en.wikipedia.org/wiki/Immunoglobulin_light_chain light chain] and each chain is composed of a variable and a constant region. The [http://en.wikipedia.org/wiki/Paratope paratope] is located in the N terminal of the variable region of the heavy and light chains of the fab. H6831 and CB2 are IgG mAbs that targets the C-terminal of OspB and LA-2 is an IgM mAb that targets the C-terminal of OspA. <ref>PMID:107164</ref>

==OspB and H6831==
<Structure load='1RJL' size='400' frame='true' align='right' caption='OspB and H6831 Fab complex' scene='Studio:G1SecL01/1/10' />

===Interaction between OspB and H6831===
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

The <scene name='Studio:G1SecL01/1/10'>OspB-H6831 complex</scene> consist of two components, the outer surface protein <scene name='Studio:G1SecL01/1/11'>OspB</scene>, and the <scene name='Studio:G1SecL01/1/12'>fab</scene>, subdivided into the <scene name='Studio:G1SecL01/1/14'>heavy chain</scene> and the <scene name='Studio:G1SecL01/1/13'>light chain</scene>. Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the <scene name='Studio:G1SecL01/1/15'>three adjacent surface-exposed loops</scene> at the C-terminal of OspB and some <scene name='Studio:G1SecL01/1/16'>residues on the fab heavy chain</scene> that include tyrosine, tryptophan, glutamate, and histidine.

The majority of hydrogen bonds and electrostatic interactions are between loop 2 (residues 250-254) and the fab heavy chain. <scene name='Studio:G1SecL01/1/17'>Lysine 253</scene> in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine and tryptophan. It also makes hydrogen bonds with the glutamate in the heavy chain of the fab and forms an ionic bond. Carbonyl in loop 1 (green link) of the OspB interacts with histidine in the fab heavy chain. <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> of OspB interacts with fab light chain. <ref name=becker>PMID:15713683</ref>.

===Structural changes to OspB in the complexed form===
The binding of H6831 to OspB leads to some conformational changes in OspB compared to its free form. Study, done by becker using crystallography, has showed that the most significant difference is the loss of the central <scene name='Studio:G1SecL01/1/19'>beta sheet</scene>, strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the Fab-binding site (residues 218 –220). In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts <ref name=becker />.

===Bactericidal action===
The fab binding destabilizes the [http://en.wikipedia.org/wiki/Bacterial_outer_membrane outer membrane] (OM) of B. burdorferi, with subsequent formation of [http://en.wikipedia.org/wiki/Spheroplast spheroplasts]. It has been observed that the bactericidal action, but not the binding, requires the presence of divalent cations (Mg2+ and Ca2+). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the divalent cations. It was speculated that OspB-Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm, and leading to the lysis of the cell <ref>Escudero; Halluska et al. 1997</ref>.

==OspA and LA-2==
<Structure load='1FJ1' size='400' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

===OspA===
OspA is 53% similar to OspB. OspA is usually undetectable in the early stages of lyme disease, because it is down regulated when OspC is expressed (provide citation). Despite the similarity between OspA and OspB, both in vivo and vitro OspB is susceptible to cleavage by exogenous [http://en.wikipedia.org/wiki/Protease proteases], whereas OspA is relatively resistant (Becker, structural). This characteristic might have contributed to OspA being a proper vaccine to lyme disease that is used to prevent transmission of B.burgodorferi from tick vector to mammalian host by complement-independent killing.<ref name=ding />

===Interaction between OspA and LA-2===
LA-2 is an IgM murine monoclonal antibody that interacts with three exposed loop on the C-terminal of OspA. These interactions include eight direct hydrogen bonds, four solvent-bridged hydrogen bonds, three ion pairs, and numerous van der Waals interactions <ref name=ding />.

===Structural changes to OspA in the complexed form===
Conformational changes upon the binding of OspA and LA-2 show that LA-2 recognition of OspA involves an induced fit mechanism where loops 1-3 conformations shift to optimize complementarity to the antigen-combining site <ref name=ding />. The overall structure of the C-terminal of OspA is unchanged upon the binding of LA-2 with comparison to the free OspA. The maximum atomic shift is 4.7Å at the site of Ser206.<ref>PMID: 11183781</ref>

References: {{reflist}}

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-30T03:00:55Z

Safa Abdelhakim:

==Introduction==
===''Borrelia burgdoferi''===

The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/ Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to certain forms of complement-dependent immune response by the evasion of the [http://en.wikipedia.org/wiki/Alternative_complement_pathway alternative complement pathway] and the blocking of complement [http://en.wikipedia.org/wiki/Complement_component_3 C3]. <ref>PMID:18080415</ref> This resistance increases the importance of the complement independent immune response when combating ''B. burgdorferi''. Certain fragment antigen binding regions ([http://en.wikipedia.org/wiki/Fragment_antigen-binding fab]) of IgG and IgM monoclonal antibodies (mAbs)are bactericidal even in the absence of complement. Binding of these fabs to their corresponding outer surface protein (OspA and OspB) of ''B. burgdoferi'' leads to the lysis of the bacteria.<ref>PMID:15864264</ref>

===Fragment Antigen Binding (fab)===
[[Image:Fab reigon.png|right|thumb|Digestion of an antibody by Papain separates the fab reigons from the antibody]]
Fab consists of a [http://en.wikipedia.org/wiki/Immunoglobulin_heavy_chain heavy chain] and [http://en.wikipedia.org/wiki/Immunoglobulin_light_chain light chain] and each chain is composed of a variable and a constant region. The [http://en.wikipedia.org/wiki/Paratope paratope] is located in the N terminal of the variable region of the heavy and light chains of the fab. H6831 and CB2 are IgG mAbs that targets the C-terminal of OspB and LA-2 is an IgM mAb that targets the C-terminal of OspA. <ref>PMID:107164</ref>

==OspB and H6831==
<Structure load='1RJL' size='400' frame='true' align='right' caption='OspB and H6831 Fab complex' scene='Studio:G1SecL01/1/10' />

===Interaction between OspB and H6831===
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

The <scene name='Studio:G1SecL01/1/10'>OspB-H6831 complex</scene> consist of two components, the outer surface protein <scene name='Studio:G1SecL01/1/11'>OspB</scene>, and the <scene name='Studio:G1SecL01/1/12'>fab</scene>, subdivided into the <scene name='Studio:G1SecL01/1/14'>heavy chain</scene> and the <scene name='Studio:G1SecL01/1/13'>light chain</scene>. Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the <scene name='Studio:G1SecL01/1/15'>three adjacent surface-exposed loops</scene> at the C-terminal of OspB and some <scene name='Studio:G1SecL01/1/16'>residues on the fab heavy chain</scene> that include tyrosine, tryptophan, glutamate, and histidine.

The majority of hydrogen bonds and electrostatic interactions are between loop 2 (residues 250-254) and the fab heavy chain. <scene name='Studio:G1SecL01/1/17'>Lysine 253</scene> in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine and tryptophan. It also makes hydrogen bonds with the glutamate in the heavy chain of the fab and forms an ionic bond. Carbonyl in loop 1 (green link) of the OspB interacts with histidine in the fab heavy chain. <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> of OspB interacts with fab light chain. <ref name=becker>PMID:15713683</ref>.

===Structural changes to OspB in the complexed form===
The binding of H6831 to OspB leads to some conformational changes in OspB compared to its free form. Study, done by becker using crystallography, has showed that the most significant difference is the loss of the central <scene name='Studio:G1SecL01/1/19'>beta sheet</scene>, strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the Fab-binding site (residues 218 –220). In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts <ref name=becker />.

====Bactericidal action====
The fab binding destabilizes the [http://en.wikipedia.org/wiki/Bacterial_outer_membrane outer membrane] (OM) of B. burdorferi, with subsequent formation of [http://en.wikipedia.org/wiki/Spheroplast spheroplasts]. It has been observed that the bactericidal action, but not the binding, requires the presence of divalent cations (Mg2+ and Ca2+). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the divalent cations. It was speculated that OspB-Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm, and leading to the lysis of the cell <ref>Escudero; Halluska et al. 1997</ref>.

==OspA and LA-2==
<Structure load='1FJ1' size='400' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>
===OspA===
OspA is 53% similar to OspB. OspA is usually undetectable in the early stages of lyme disease, because it is down regulated when OspC is expressed (provide citation). Despite the similarity between OspA and OspB, both in vivo and vitro OspB is susceptible to cleavage by exogenous [http://en.wikipedia.org/wiki/Protease proteases], whereas OspA is relatively resistant (Becker, structural). This characteristic might have contributed to OspA being a proper vaccine to lyme disease that is used to prevent transmission of B.burgodorferi from tick vector to mammalian host by complement-independent killing.<ref name=ding />
===Interaction between OspA and LA-2===
LA-2 is an IgM murine monoclonal antibody that interacts with three exposed loop on the C-terminal of OspA. These interactions include eight direct hydrogen bonds, four solvent-bridged hydrogen bonds, three ion pairs, and numerous van der Waals interactions <ref name=ding />.
===Structural changes to OspA in the complexed form===
Conformational changes upon the binding of OspA and LA-2 show that LA-2 recognition of OspA involves an induced fit mechanism where loops 1-3 conformations shift to optimize complementarity to the antigen-combining site <ref name=ding />. The overall structure of the C-terminal of OspA is unchanged upon the binding of LA-2 with comparison to the free OspA. The maximum atomic shift is 4.7Å at the site of Ser206.<ref>PMID: 11183781</ref>

References: {{reflist}}

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-30T02:36:51Z

Safa Abdelhakim:

==Introduction==
===''Borrelia burgdoferi''===

The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/ Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to certain forms of complement-dependent immune response by the evasion of the [http://en.wikipedia.org/wiki/Alternative_complement_pathway alternative complement pathway] and the blocking of complement [http://en.wikipedia.org/wiki/Complement_component_3 C3]. <ref>PMID:18080415</ref> This resistance increases the importance of the complement independent immune response when combating ''B. burgdorferi''. Certain fragment antigen binding regions ([http://en.wikipedia.org/wiki/Fragment_antigen-binding fab]) of IgG and IgM monoclonal antibodies (mAbs)are bactericidal even in the absence of complement. Binding of these fabs to their corresponding outer surface protein (OspA and OspB) of ''B. burgdoferi'' leads to the lysis of the bacteria.<ref>PMID:15864264</ref>

===Fragment Antigen Binding (fab)===
[[Image:Fab reigon.png|right|thumb|Digestion of an antibody by Papain separates the fab reigons from the antibody]]
Fab consists of a [http://en.wikipedia.org/wiki/Immunoglobulin_heavy_chain heavy chain] and [http://en.wikipedia.org/wiki/Immunoglobulin_light_chain light chain] and each chain is composed of a variable and a constant region. The [http://en.wikipedia.org/wiki/Paratope paratope] is located in the N terminal of the variable region of the heavy and light chains of the fab. H6831 and CB2 are IgG mAbs that targets the C-terminal of OspB and LA-2 is an IgM mAb that targets the C-terminal of OspA. <ref>PMID:107164</ref>

==OspB and H6831==
<Structure load='1RJL' size='400' frame='true' align='right' caption='OspB and H6831 Fab complex' scene='Studio:G1SecL01/1/10' />

===Interaction between OspB and H6831===
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

The <scene name='Studio:G1SecL01/1/10'>OspB-H6831 complex</scene> consist of two components, the outer surface protein <scene name='Studio:G1SecL01/1/11'>OspB</scene>, and the <scene name='Studio:G1SecL01/1/12'>fab</scene>, subdivided into the <scene name='Studio:G1SecL01/1/14'>heavy chain</scene> and the <scene name='Studio:G1SecL01/1/13'>light chain</scene>. Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the <scene name='Studio:G1SecL01/1/15'>three adjacent surface-exposed loops</scene> at the C-terminal of OspB and some <scene name='Studio:G1SecL01/1/16'>residues on the fab heavy chain</scene> that include tyrosine, tryptophan, glutamate, and histidine.

The majority of hydrogen bonds and electrostatic interactions are between loop 2 (residues 250-254) and the fab heavy chain. <scene name='Studio:G1SecL01/1/17'>Lysine 253</scene> in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine and tryptophan. It also makes hydrogen bonds with the glutamate in the heavy chain of the fab and forms an ionic bond. Carbonyl in loop 1 (green link) of the OspB interacts with histidine in the fab heavy chain. <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> of OspB interacts with fab light chain. <ref name=becker>PMID:15713683</ref>.

===Structural to OspB in the complexed form===
The binding of H6831 to OspB leads to some conformational changes in OspB compared to its free form. Study, done by becker using crystallography, has showed that the most significant difference is the loss of the central <scene name='Studio:G1SecL01/1/19'>beta sheet</scene>, strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the Fab-binding site (residues 218 –220). In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts <ref name=becker />.

====Requirements for the Bactericidal Effect and Proposed Mechanism====
The fab binding destabilizes the [http://en.wikipedia.org/wiki/Bacterial_outer_membrane outer membrane] (OM) of B. burdorferi, with subsequent formation of [http://en.wikipedia.org/wiki/Spheroplast spheroplasts]. It has been observed that the bactericidal action, but not the binding, requires the presence of divalent cations (Mg2+ and Ca2+). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the divalent cations. It was speculated that OspB-Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm, and leading to the lysis of the cell <ref>Escudero; Halluska et al. 1997</ref>.

==OspA and LA-2==
<Structure load='1FJ1' size='400' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />
===OspA===
OspA is 53% similar to OspB. OspA is usually undetectable in the early stages of lyme disease, because it is down regulated when OspC is expressed (provide citation). Despite the similarity between OspA and OspB, both in vivo and vitro OspB is susceptible to cleavage by exogenous [http://en.wikipedia.org/wiki/Protease proteases], whereas OspA is relatively resistant (Becker, structural). This characteristic may have contributed to OspA being a better vaccine to lyme disease that is used to prevent transmission of B.burgodorferi from tick vector to mammalian host by complement-independent killing.<ref name=ding />
===Interaction between OspA and LA-2===
LA-2 is an IgM murine monoclonal antibody that interacts with three exposed loop on the C-terminal of OspA. These interactions include eight direct hydrogen bonds, four solvent-bridged hydrogen bonds, three ion pairs, and numerous van der Waals interactions <ref name=ding />.
===Conformational changes===
Conformational changes upon the binding of OspA and LA-2 show that LA-2 recognition of OspA involves an induced fit mechanism where loops 1-3 conformations shift to optimize complementarity to the antigen-combining site <ref name=ding />. The overall structure of the C-terminal of OspA is unchanged upon the binding of LA-2 with comparison to the free OspA, except for the minor shift to accommodate for the binding. The maximum atomic shift is 4.7A at the site of Ser206.<ref>PMID: 11183781</ref>

<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

References: {{reflist}}

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-30T02:27:34Z

Safa Abdelhakim:

==Introduction==
===''Borrelia burgdoferi''===

The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/ Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to certain forms of complement-dependent immune response by the evasion of the [http://en.wikipedia.org/wiki/Alternative_complement_pathway alternative complement pathway] and the blocking of complement [http://en.wikipedia.org/wiki/Complement_component_3 C3]. <ref>PMID:18080415</ref> This resistance increases the importance of the complement independent immune response when combating ''B. burgdorferi''. Certain fragment antigen binding regions ([http://en.wikipedia.org/wiki/Fragment_antigen-binding fab]) of IgG and IgM monoclonal antibodies (mAbs)are bactericidal even in the absence of complement. Binding of these fabs to their corresponding outer surface protein (OspA and OspB) of ''B. burgdoferi'' leads to the lysis of the bacteria.<ref>PMID:15864264</ref>

===Fragment Antigen Binding (fab)===
[[Image:Fab reigon.png|right|thumb|Digestion of an antibody by Papain separates the fab reigons from the antibody]]
Fab consists of a [http://en.wikipedia.org/wiki/Immunoglobulin_heavy_chain heavy chain] and [http://en.wikipedia.org/wiki/Immunoglobulin_light_chain light chain] and each chain is composed of a variable and a constant region. The [http://en.wikipedia.org/wiki/Paratope paratope] is located in the N terminal of the variable region of the heavy and light chains of the fab. H6831 and CB2 are IgG mAbs that targets the C-terminal of OspB and LA-2 is an IgM mAb that targets the C-terminal of OspA. <ref>PMID:107164</ref>

==OspB and H6831==
<Structure load='1RJL' size='400' frame='true' align='right' caption='OspB and H6831 Fab complex' scene='Studio:G1SecL01/1/10' />

===Complex Interaction between OspB and H6831===
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

The <scene name='Studio:G1SecL01/1/10'>OspB-H6831 complex</scene> consist of two components, the outer surface protein <scene name='Studio:G1SecL01/1/11'>OspB</scene>, and the <scene name='Studio:G1SecL01/1/12'>fab</scene>, subdivided into the <scene name='Studio:G1SecL01/1/14'>heavy chain</scene> and the <scene name='Studio:G1SecL01/1/13'>light chain</scene>. Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the <scene name='Studio:G1SecL01/1/15'>three adjacent surface-exposed loops</scene> at the C-terminal of OspB and some <scene name='Studio:G1SecL01/1/16'>residues on the fab heavy chain</scene> that include tyrosine, tryptophan, glutamate, and histidine.

The majority of hydrogen bonds and electrostatic interactions are between loop 2 (residues 250-254) and the fab heavy chain. <scene name='Studio:G1SecL01/1/17'>Lysine 253</scene> in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine and tryptophan. It also makes hydrogen bonds with the glutamate in the heavy chain of the fab and forms an ionic bond. Carbonyl in loop 1 (green link) of the OspB interacts with histidine in the fab heavy chain. <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> of OspB interacts with fab light chain. <ref name=becker>PMID:15713683</ref>.

===Structural Changes to the complexed OspB===
The binding leads to some conformational changes in OspB compared to its free form. Study, done by becker using crystallography, has showed the most significant difference is the loss of the central <scene name='Studio:G1SecL01/1/19'>beta sheet</scene> strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the Fab-binding site (residues 218 –220). In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts <ref name=becker />.

====Requirements for the Bactericidal Effect and Proposed Mechanism====
The fab binding destabilizes the [http://en.wikipedia.org/wiki/Bacterial_outer_membrane outer membrane] (OM) of B. burdorferi, with subsequent formation of [http://en.wikipedia.org/wiki/Spheroplast spheroplasts]. It has been observed that the bactericidal action, but not the binding, requires the presence of bivalent cations (Mg2+ and Ca2+). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the bivalent cations. It was speculated that OspB- Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>Escudero; Halluska et al. 1997</ref>.
Need to be rephrased and squeezed and may be a sentence about the cholestrol needs to be added and if there is a specific function for the charge triad it may be added

==OspA and LA-2==
<Structure load='1FJ1' size='400' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />
===OspA===
OspA is 53% similar to OspB. OspA is usually undetectable in the early stages of lyme disease, because it is down regulated when OspC is expressed (provide citation). Despite the similarity between OspA and OspB, both in vivo and vitro OspB is susceptible to cleavage by exogenous [http://en.wikipedia.org/wiki/Protease proteases], whereas OspA is relatively resistant (Becker, structural). This characteristic may have contributed to OspA being a better vaccine to lyme disease that is used to prevent transmission of B.burgodorferi from tick vector to mammalian host by complement-independent killing.<ref name=ding />
===Interaction between OspA and LA-2===
LA-2 is an IgM murine monoclonal antibody that interacts with three exposed loop on the C-terminal of OspA. These interactions include eight direct hydrogen bonds, four solvent-bridged hydrogen bonds, three ion pairs, and numerous van der Waals interactions <ref name=ding />.
===Conformational changes===
Conformational changes upon the binding of OspA and LA-2 show that LA-2 recognition of OspA involves an induced fit mechanism where loops 1-3 conformations shift to optimize complementarity to the antigen-combining site <ref name=ding />. The overall structure of the C-terminal of OspA is unchanged upon the binding of LA-2 with comparison to the free OspA, except for the minor shift to accommodate for the binding. The maximum atomic shift is 4.7A at the site of Ser206.<ref>PMID: 11183781</ref>

<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

References: {{reflist}}

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-30T02:18:41Z

Safa Abdelhakim:

==Introduction==
===''Borrelia burgdoferi''===

The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/ Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to certain forms of complement-dependent immune response by the evasion of the [http://en.wikipedia.org/wiki/Alternative_complement_pathway alternative complement pathway] and the blocking of complement [http://en.wikipedia.org/wiki/Complement_component_3 C3]. <ref>PMID:18080415</ref> This resistance increases the importance of the complement independent immune response when combating ''B. burgdorferi''. Certain fragment antigen binding regions ([http://en.wikipedia.org/wiki/Fragment_antigen-binding fab]) of IgG and IgM monoclonal antibodies (mAbs)are bactericidal even in the absence of complement. Binding of these fabs to their corresponding outer surface protein (OspA and OspB) of ''B. burgdoferi'' leads to the lysis of the bacteria.<ref>PMID:15864264</ref>

===Fragment Antigen Binding (fab)===
[[Image:Fab reigon.png|right|thumb|Digestion of an antibody by Papain separates the fab reigons from the antibody]]
Fab consists of a [http://en.wikipedia.org/wiki/Immunoglobulin_heavy_chain heavy chain] and [http://en.wikipedia.org/wiki/Immunoglobulin_light_chain light chain] and each chain is composed of a variable and a constant region. The [http://en.wikipedia.org/wiki/Paratope paratope] is located in the N terminal of the variable region of the heavy and light chains of the fab. H6831 and CB2 are IgG mAbs that targets the C-terminal of OspB and LA-2 is an IgM mAb that targets the C-terminal of OspA. <ref>PMID:107164</ref>

==OspB and H6831==
<Structure load='1RJL' size='400' frame='true' align='right' caption='OspB and H6831 Fab complex' scene='Studio:G1SecL01/1/10' />

===Complex Interaction between OspB and H6831===
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

The <scene name='Studio:G1SecL01/1/10'>OspB-H6831 complex</scene> consist of two components, the outer surface protein <scene name='Studio:G1SecL01/1/11'>OspB</scene>, and the <scene name='Studio:G1SecL01/1/12'>fab</scene>, subdivided into the <scene name='Studio:G1SecL01/1/14'>heavy chain</scene> and the <scene name='Studio:G1SecL01/1/13'>light chain</scene>. Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the <scene name='Studio:G1SecL01/1/15'>three adjacent surface-exposed loops</scene> at the C-terminal of OspB and some <scene name='Studio:G1SecL01/1/16'>residues on the fab heavy chain</scene> that include tyrosine, tryptophan, glutamate, and histidine.

The majority of hydrogen bonds and electrostatic interactions are between loop 2 (residues 250-254) and the fab heavy chain. <scene name='Studio:G1SecL01/1/17'>Lysine 253</scene> in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine and tryptophan. It also makes hydrogen bonds with the glutamate in the heavy chain of the fab and forms an ionic bond. Carbonyl in loop 1 (green link) of the OspB interacts with histidine in the fab heavy chain. <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> of OspB interacts with fab light chain. <ref name=becker>PMID:15713683</ref>.

===Conformational Changes to OspB===
The binding leads to some conformational changes in OspB. Whereas Ding et al.<ref name=ding>PMID:11183781</ref> found no changes in the C-terminal of OspA upon the binding to the fab. The most significant difference between the free and the complexed structure of OspB is the loss of the central <scene name='Studio:G1SecL01/1/19'>beta sheet</scene> strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the Fab-binding site (residues 218 –220). In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts <ref name=becker />.

====Requirements for the Bactericidal Effect and Proposed Mechanism====
The fab binding destabilizes the [http://en.wikipedia.org/wiki/Bacterial_outer_membrane outer membrane] (OM) of B. burdorferi, with subsequent formation of [http://en.wikipedia.org/wiki/Spheroplast spheroplasts]. It has been observed that the bactericidal action, but not the binding, requires the presence of bivalent cations (Mg2+ and Ca2+). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the bivalent cations. It was speculated that OspB- Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>Escudero; Halluska et al. 1997</ref>.
Need to be rephrased and squeezed and may be a sentence about the cholestrol needs to be added and if there is a specific function for the charge triad it may be added

==OspA and LA-2==
<Structure load='1FJ1' size='400' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />
===OspA===
OspA is 53% similar to OspB. OspA is usually undetectable in the early stages of lyme disease, because it is down regulated when OspC is expressed (provide citation). Despite the similarity between OspA and OspB, both in vivo and vitro OspB is susceptible to cleavage by exogenous [http://en.wikipedia.org/wiki/Protease proteases], whereas OspA is relatively resistant (Becker, structural). This characteristic may have contributed to OspA being a better vaccine to lyme disease that is used to prevent transmission of B.burgodorferi from tick vector to mammalian host by complement-independent killing.<ref name=ding />
===Interaction between OspA and LA-2===
LA-2 is an IgM murine monoclonal antibody that interacts with three exposed loop on the C-terminal of OspA. These interactions include eight direct hydrogen bonds, four solvent-bridged hydrogen bonds, three ion pairs, and numerous van der Waals interactions <ref name=ding />.
===Conformational changes===
Conformational changes upon the binding of OspA and LA-2 show that LA-2 recognition of OspA involves an induced fit mechanism where loops 1-3 conformations shift to optimize complementarity to the antigen-combining site <ref name=ding />. The overall structure of the C-terminal of OspA is unchanged upon the binding of LA-2 with comparison to the free OspA, except for the minor shift to accommodate for the binding. The maximum atomic shift is 4.7A at the site of Ser206.<ref>PMID: 11183781</ref>

<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

References: {{reflist}}

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-30T02:14:19Z

Safa Abdelhakim:

==Introduction==
===''Borrelia burgdoferi''===

The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/ Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to certain forms of complement-dependent immune response by the evasion of the [http://en.wikipedia.org/wiki/Alternative_complement_pathway alternative complement pathway] and the blocking of complement [http://en.wikipedia.org/wiki/Complement_component_3 C3]. <ref>PMID:18080415</ref> This resistance increases the importance of the complement independent immune response when combating ''B. burgdorferi''. Certain fragment antigen binding regions ([http://en.wikipedia.org/wiki/Fragment_antigen-binding fab]) of IgG and IgM monoclonal antibodies (mAbs)are bactericidal even in the absence of complement. Binding of these fabs to their corresponding outer surface protein (OspA and OspB) of ''B. burgdoferi'' leads to the lysis of the bacteria.<ref>PMID:15864264</ref>

===Fragment Antigen Binding (fab)===
[[Image:Fab reigon.png|right|thumb|Digestion of an antibody by Papain separates the fab reigons from the antibody]]
Fab consists of a [http://en.wikipedia.org/wiki/Immunoglobulin_heavy_chain heavy chain] and [http://en.wikipedia.org/wiki/Immunoglobulin_light_chain light chain] and each chain is composed of a variable and a constant region. The [http://en.wikipedia.org/wiki/Paratope paratope] is located in the N terminal of the variable region of the heavy and light chains of the fab. H6831 and CB2 are IgG mAbs that targets the C-terminal of OspB and LA-2 is an IgM mAb that targets the C-terminal of OspA. <ref>PMID:107164</ref>

==OspB and H6831==
<Structure load='1RJL' size='400' frame='true' align='right' caption='OspB and H6831 Fab complex' scene='Studio:G1SecL01/1/10' />

===Complex Interaction between OspB and H6831===
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

The <scene name='Studio:G1SecL01/1/10'>OspB-H6831 complex</scene> consist of two components, the outer surface protein <scene name='Studio:G1SecL01/1/11'>OspB</scene>, and the <scene name='Studio:G1SecL01/1/12'>fab</scene>, subdivided into the <scene name='Studio:G1SecL01/1/14'>heavy chain</scene> and the <scene name='Studio:G1SecL01/1/13'>light chain</scene>. Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the <scene name='Studio:G1SecL01/1/15'>three adjacent surface-exposed loops</scene> at the C-terminal of OspB and some <scene name='Studio:G1SecL01/1/16'>residues on the fab heavy chain</scene> that include tyrosine, tryptophan, glutamate, and histidine.

The majority of the electrostatic and hydrogen-bonded interactions are between loop 2 (residues 250-254) and the fab heavy chain. <scene name='Studio:G1SecL01/1/17'>Lysine 253</scene> in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine (green link) and tryptophan (green link). It also makes hydrogen bonds with the glutamate (green link) in the heavy chain of the fab and forms an ionic bond. Carbonyl in loop 1 (green link) of the OspB interacts with histidine in the fab heavy chain. <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> of OspB interacts with fab light chain. <ref name=becker>PMID:15713683</ref>.

===Conformational Changes to OspB===
The binding leads to some conformational changes in OspB. Whereas Ding et al.<ref name=ding>PMID:11183781</ref> found no changes in the C-terminal of OspA upon the binding to the fab. The most significant difference between the free and the complexed structure of OspB is the loss of the central <scene name='Studio:G1SecL01/1/19'>beta sheet</scene> strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the Fab-binding site (residues 218 –220). In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts <ref name=becker />.

====Requirements for the Bactericidal Effect and Proposed Mechanism====
The fab binding destabilizes the [http://en.wikipedia.org/wiki/Bacterial_outer_membrane outer membrane] (OM) of B. burdorferi, with subsequent formation of [http://en.wikipedia.org/wiki/Spheroplast spheroplasts]. It has been observed that the bactericidal action, but not the binding, requires the presence of bivalent cations (Mg2+ and Ca2+). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the bivalent cations. It was speculated that OspB- Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>Escudero; Halluska et al. 1997</ref>.
Need to be rephrased and squeezed and may be a sentence about the cholestrol needs to be added and if there is a specific function for the charge triad it may be added

==OspA and LA-2==
<Structure load='1FJ1' size='400' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />
===OspA===
OspA is 53% similar to OspB. OspA is usually undetectable in the early stages of lyme disease, because it is down regulated when OspC is expressed (provide citation). Despite the similarity between OspA and OspB, both in vivo and vitro OspB is susceptible to cleavage by exogenous [http://en.wikipedia.org/wiki/Protease proteases], whereas OspA is relatively resistant (Becker, structural). This characteristic may have contributed to OspA being a better vaccine to lyme disease that is used to prevent transmission of B.burgodorferi from tick vector to mammalian host by complement-independent killing.<ref name=ding />
===Interaction between OspA and LA-2===
LA-2 is an IgM murine monoclonal antibody that interacts with three exposed loop on the C-terminal of OspA. These interactions include eight direct hydrogen bonds, four solvent-bridged hydrogen bonds, three ion pairs, and numerous van der Waals interactions <ref name=ding />.
===Conformational changes===
Conformational changes upon the binding of OspA and LA-2 show that LA-2 recognition of OspA involves an induced fit mechanism where loops 1-3 conformations shift to optimize complementarity to the antigen-combining site <ref name=ding />. The overall structure of the C-terminal of OspA is unchanged upon the binding of LA-2 with comparison to the free OspA, except for the minor shift to accommodate for the binding. The maximum atomic shift is 4.7A at the site of Ser206.<ref>PMID: 11183781</ref>

<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

References: {{reflist}}

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-30T02:00:34Z

Safa Abdelhakim:

==Introduction==
===''Borrelia burgdoferi''===

The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/ Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to certain forms of complement-dependent immune response by the evasion of the [http://en.wikipedia.org/wiki/Alternative_complement_pathway alternative complement pathway] and the blocking of complement [http://en.wikipedia.org/wiki/Complement_component_3 C3]. <ref>PMID:18080415</ref> This resistance increases the importance of the complement independent immune response when combating ''B. burgdorferi''. Certain fragment antigen binding regions ([http://en.wikipedia.org/wiki/Fragment_antigen-binding fab]) of IgG and IgM monoclonal antibodies (mAbs)are bactericidal even in the absence of complement. Binding of these fabs to their corresponding outer surface protein (OspA and OspB) of ''B. burgdoferi'' leads to the lysis of the bacteria.<ref>PMID:15864264</ref>

===Fragment Antigen Binding (fab)===
[[Image:Fab reigon.png|right|thumb|Digestion of an antibody by Papain separates the fab reigons from the antibody]]
Fab consists of a [http://en.wikipedia.org/wiki/Immunoglobulin_heavy_chain heavy chain] and [http://en.wikipedia.org/wiki/Immunoglobulin_light_chain light chain] and each chain is composed of a variable and a constant region. The [http://en.wikipedia.org/wiki/Paratope paratope] is located in the N terminal of the variable region of the heavy and light chains of the fab. H6831 and CB2 are IgG mAbs that targets the C-terminal of OspB and LA-2 is an IgM mAb that targets the C-terminal of OspA. <ref>PMID:107164</ref>

==OspB and H6831==
<Structure load='1RJL' size='400' frame='true' align='right' caption='OspB and H6831 Fab complex' scene='Studio:G1SecL01/1/10' />

===Complex Interaction between OspB and H6831===
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

The <scene name='Studio:G1SecL01/1/10'>OspB-H6831 complex</scene> consist of two main components, the outer surface protein <scene name='Studio:G1SecL01/1/11'>OspB</scene>, and the <scene name='Studio:G1SecL01/1/12'>fab</scene>, subdivided into the <scene name='Studio:G1SecL01/1/14'>heavy chain</scene> and the <scene name='Studio:G1SecL01/1/13'>light chain</scene>. Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the <scene name='Studio:G1SecL01/1/15'>three adjacent surface-exposed loops</scene> at the C-terminal of OspB and some <scene name='Studio:G1SecL01/1/16'>residues</scene> on the fab heavy chain that include tyrosine, tryptophan, glutamate, and histidine.

The majority of the electrostatic and hydrogen-bonded interactions are between loop 2 (residues 250-254) and the fab heavy chain. <scene name='Studio:G1SecL01/1/17'>Lysine 253</scene> in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine (green link) and tryptophan (green link). It also makes hydrogen bonds with the glutamate (green link) in the heavy chain of the fab and forms an ionic bond. Carbonyl in loop 1 (green link) of the OspB interacts with histidine in the fab heavy chain. <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> of OspB interacts with fab light chain. <ref name=becker>PMID:15713683</ref>.

===Conformational Changes to OspB===
The binding leads to some conformational changes in OspB. Whereas Ding et al.<ref name=ding>PMID:11183781</ref> found no changes in the C-terminal of OspA upon the binding to the fab. The most significant difference between the free and the complexed structure of OspB is the loss of the central <scene name='Studio:G1SecL01/1/19'>beta sheet</scene> strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the Fab-binding site (residues 218 –220). In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts <ref name=becker />.

====Requirements for the Bactericidal Effect and Proposed Mechanism====
The fab binding destabilizes the [http://en.wikipedia.org/wiki/Bacterial_outer_membrane outer membrane] (OM) of B. burdorferi, with subsequent formation of [http://en.wikipedia.org/wiki/Spheroplast spheroplasts]. It has been observed that the bactericidal action, but not the binding, requires the presence of bivalent cations (Mg2+ and Ca2+). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the bivalent cations. It was speculated that OspB- Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>Escudero; Halluska et al. 1997</ref>.
Need to be rephrased and squeezed and may be a sentence about the cholestrol needs to be added and if there is a specific function for the charge triad it may be added

==OspA and LA-2==
<Structure load='1FJ1' size='400' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />
===OspA===
OspA is 53% similar to OspB. OspA is usually undetectable in the early stages of lyme disease, because it is down regulated when OspC is expressed (provide citation). Despite the similarity between OspA and OspB, both in vivo and vitro OspB is susceptible to cleavage by exogenous [http://en.wikipedia.org/wiki/Protease proteases], whereas OspA is relatively resistant (Becker, structural). This characteristic may have contributed to OspA being a better vaccine to lyme disease that is used to prevent transmission of B.burgodorferi from tick vector to mammalian host by complement-independent killing.<ref name=ding />
===Interaction between OspA and LA-2===
LA-2 is an IgM murine monoclonal antibody that interacts with three exposed loop on the C-terminal of OspA. These interactions include eight direct hydrogen bonds, four solvent-bridged hydrogen bonds, three ion pairs, and numerous van der Waals interactions <ref name=ding />.
===Conformational changes===
Conformational changes upon the binding of OspA and LA-2 show that LA-2 recognition of OspA involves an induced fit mechanism where loops 1-3 conformations shift to optimize complementarity to the antigen-combining site <ref name=ding />. The overall structure of the C-terminal of OspA is unchanged upon the binding of LA-2 with comparison to the free OspA, except for the minor shift to accommodate for the binding. The maximum atomic shift is 4.7A at the site of Ser206.<ref>PMID: 11183781</ref>

<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

References: {{reflist}}

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-30T01:59:52Z

Safa Abdelhakim:

==Introduction==
===''Borrelia burgdoferi''===

The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/ Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to certain forms of complement-dependent immune response by the evasion of the [http://en.wikipedia.org/wiki/Alternative_complement_pathway alternative complement pathway] and the blocking of complement [http://en.wikipedia.org/wiki/Complement_component_3 C3]. <ref>PMID:18080415</ref> This resistance increases the importance of the complement independent immune response when combating ''B. burgdorferi''. Certain fragment antigen binding regions ([http://en.wikipedia.org/wiki/Fragment_antigen-binding fab]) of IgG and IgM monoclonal antibodies (mAbs)are bactericidal even in the absence of complement. Binding of these fabs to their corresponding outer surface protein (OspA and OspB) of ''B. burgdoferi'' leads to the lysis of the bacteria.<ref>PMID:15864264</ref>

===Fragment Antigen Binding (fab) Reigon===
[[Image:Fab reigon.png|right|thumb|Digestion of an antibody by Papain separates the fab reigons from the antibody]]
Fab consists of a [http://en.wikipedia.org/wiki/Immunoglobulin_heavy_chain heavy chain] and [http://en.wikipedia.org/wiki/Immunoglobulin_light_chain light chain] and each chain is composed of a variable and a constant region. The [http://en.wikipedia.org/wiki/Paratope paratope] is located in the N terminal of the variable region of the heavy and light chains of the fab. H6831 and CB2 are IgG mAbs that targets the C-terminal of OspB and LA-2 is an IgM mAb that targets the C-terminal of OspA. <ref>PMID:107164</ref>

==OspB and H6831==
<Structure load='1RJL' size='400' frame='true' align='right' caption='OspB and H6831 Fab complex' scene='Studio:G1SecL01/1/10' />

===Complex Interaction between OspB and H6831===
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

The <scene name='Studio:G1SecL01/1/10'>OspB-H6831 complex</scene> consist of two main components, the outer surface protein <scene name='Studio:G1SecL01/1/11'>OspB</scene>, and the <scene name='Studio:G1SecL01/1/12'>fab</scene>, subdivided into the <scene name='Studio:G1SecL01/1/14'>heavy chain</scene> and the <scene name='Studio:G1SecL01/1/13'>light chain</scene>. Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the <scene name='Studio:G1SecL01/1/15'>three adjacent surface-exposed loops</scene> at the C-terminal of OspB and some <scene name='Studio:G1SecL01/1/16'>residues</scene> on the fab heavy chain that include tyrosine, tryptophan, glutamate, and histidine.

The majority of the electrostatic and hydrogen-bonded interactions are between loop 2 (residues 250-254) and the fab heavy chain. <scene name='Studio:G1SecL01/1/17'>Lysine 253</scene> in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine (green link) and tryptophan (green link). It also makes hydrogen bonds with the glutamate (green link) in the heavy chain of the fab and forms an ionic bond. Carbonyl in loop 1 (green link) of the OspB interacts with histidine in the fab heavy chain. <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> of OspB interacts with fab light chain. <ref name=becker>PMID:15713683</ref>.

===Conformational Changes to OspB===
The binding leads to some conformational changes in OspB. Whereas Ding et al.<ref name=ding>PMID:11183781</ref> found no changes in the C-terminal of OspA upon the binding to the fab. The most significant difference between the free and the complexed structure of OspB is the loss of the central <scene name='Studio:G1SecL01/1/19'>beta sheet</scene> strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the Fab-binding site (residues 218 –220). In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts <ref name=becker />.

====Requirements for the Bactericidal Effect and Proposed Mechanism====
The fab binding destabilizes the [http://en.wikipedia.org/wiki/Bacterial_outer_membrane outer membrane] (OM) of B. burdorferi, with subsequent formation of [http://en.wikipedia.org/wiki/Spheroplast spheroplasts]. It has been observed that the bactericidal action, but not the binding, requires the presence of bivalent cations (Mg2+ and Ca2+). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the bivalent cations. It was speculated that OspB- Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>Escudero; Halluska et al. 1997</ref>.
Need to be rephrased and squeezed and may be a sentence about the cholestrol needs to be added and if there is a specific function for the charge triad it may be added

==OspA and LA-2==
<Structure load='1FJ1' size='400' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />
===OspA===
OspA is 53% similar to OspB. OspA is usually undetectable in the early stages of lyme disease, because it is down regulated when OspC is expressed (provide citation). Despite the similarity between OspA and OspB, both in vivo and vitro OspB is susceptible to cleavage by exogenous [http://en.wikipedia.org/wiki/Protease proteases], whereas OspA is relatively resistant (Becker, structural). This characteristic may have contributed to OspA being a better vaccine to lyme disease that is used to prevent transmission of B.burgodorferi from tick vector to mammalian host by complement-independent killing.<ref name=ding />
===Interaction between OspA and LA-2===
LA-2 is an IgM murine monoclonal antibody that interacts with three exposed loop on the C-terminal of OspA. These interactions include eight direct hydrogen bonds, four solvent-bridged hydrogen bonds, three ion pairs, and numerous van der Waals interactions <ref name=ding />.
===Conformational changes===
Conformational changes upon the binding of OspA and LA-2 show that LA-2 recognition of OspA involves an induced fit mechanism where loops 1-3 conformations shift to optimize complementarity to the antigen-combining site <ref name=ding />. The overall structure of the C-terminal of OspA is unchanged upon the binding of LA-2 with comparison to the free OspA, except for the minor shift to accommodate for the binding. The maximum atomic shift is 4.7A at the site of Ser206.<ref>PMID: 11183781</ref>

<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

References: {{reflist}}

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-30T01:49:24Z

Safa Abdelhakim:

==Introduction==
===''Borrelia burgdoferi''===

The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/ Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to certain forms of complement-dependent immune response by the evasion of the [http://en.wikipedia.org/wiki/Alternative_complement_pathway alternative complement pathway] and the blocking of complement [http://en.wikipedia.org/wiki/Complement_component_3 C3]. <ref>PMID:18080415</ref> This resistance increases the importance of the complement independent immune response when combating ''B. burgdorferi''. Certain fragment antigen binding regions ([http://en.wikipedia.org/wiki/Fragment_antigen-binding fab]) of IgG and IgM monoclonal antibodies are bactericidal even in the absence of complement. Binding of these fabs to their corresponding outer surface protein (OspA and OspB) of ''B. burgdoferi'' leads to the lysis of the bacteria.<ref>PMID:15864264</ref>

===Fragment Antigen Binding (fab) Reigon===
[[Image:Fab reigon.png|right|thumb|Digestion of an antibody by Papain separates the fab reigons from the antibody]]
Fab consists of a [http://en.wikipedia.org/wiki/Immunoglobulin_heavy_chain heavy chain] and [http://en.wikipedia.org/wiki/Immunoglobulin_light_chain light chain] and each chain is composed of a variable and a constant region. The [http://en.wikipedia.org/wiki/Paratope paratope] is located in the N terminal of the variable region of the heavy and light chains. The complement-independent fab regions that interact with these outer surface proteins are LA-2, which targets the C-terminal of OspA, and CB2 and H6831, which target the C-terminal of OspB. <ref>PMID:107164</ref>

==OspB and H6831==
<Structure load='1RJL' size='400' frame='true' align='right' caption='OspB and H6831 Fab complex' scene='Studio:G1SecL01/1/10' />

===Complex Interaction between OspB and H6831===
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

The <scene name='Studio:G1SecL01/1/10'>OspB-H6831 complex</scene> consist of two main components, the outer surface protein <scene name='Studio:G1SecL01/1/11'>OspB</scene>, and the <scene name='Studio:G1SecL01/1/12'>fab</scene>, subdivided into the <scene name='Studio:G1SecL01/1/14'>heavy chain</scene> and the <scene name='Studio:G1SecL01/1/13'>light chain</scene>. Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the <scene name='Studio:G1SecL01/1/15'>three adjacent surface-exposed loops</scene> at the C-terminal of OspB and some <scene name='Studio:G1SecL01/1/16'>residues</scene> on the fab heavy chain that include tyrosine, tryptophan, glutamate, and histidine.

The majority of the electrostatic and hydrogen-bonded interactions are between loop 2 (residues 250-254) and the fab heavy chain. <scene name='Studio:G1SecL01/1/17'>Lysine 253</scene> in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine (green link) and tryptophan (green link). It also makes hydrogen bonds with the glutamate (green link) in the heavy chain of the fab and forms an ionic bond. Carbonyl in loop 1 (green link) of the OspB interacts with histidine in the fab heavy chain. <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> of OspB interacts with fab light chain. <ref name=becker>PMID:15713683</ref>.

===Conformational Changes to OspB===
The binding leads to some conformational changes in OspB. Whereas Ding et al.<ref name=ding>PMID:11183781</ref> found no changes in the C-terminal of OspA upon the binding to the fab. The most significant difference between the free and the complexed structure of OspB is the loss of the central <scene name='Studio:G1SecL01/1/19'>beta sheet</scene> strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the Fab-binding site (residues 218 –220). In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts <ref name=becker />.

====Requirements for the Bactericidal Effect and Proposed Mechanism====
The fab binding destabilizes the [http://en.wikipedia.org/wiki/Bacterial_outer_membrane outer membrane] (OM) of B. burdorferi, with subsequent formation of [http://en.wikipedia.org/wiki/Spheroplast spheroplasts]. It has been observed that the bactericidal action, but not the binding, requires the presence of bivalent cations (Mg2+ and Ca2+). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the bivalent cations. It was speculated that OspB- Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>Escudero; Halluska et al. 1997</ref>.
Need to be rephrased and squeezed and may be a sentence about the cholestrol needs to be added and if there is a specific function for the charge triad it may be added

==OspA and LA-2==
<Structure load='1FJ1' size='400' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />
===OspA===
OspA is 53% similar to OspB. OspA is usually undetectable in the early stages of lyme disease, because it is down regulated when OspC is expressed (provide citation). Despite the similarity between OspA and OspB, both in vivo and vitro OspB is susceptible to cleavage by exogenous [http://en.wikipedia.org/wiki/Protease proteases], whereas OspA is relatively resistant (Becker, structural). This characteristic may have contributed to OspA being a better vaccine to lyme disease that is used to prevent transmission of B.burgodorferi from tick vector to mammalian host by complement-independent killing.<ref name=ding />
===Interaction between OspA and LA-2===
LA-2 is an IgM murine monoclonal antibody that interacts with three exposed loop on the C-terminal of OspA. These interactions include eight direct hydrogen bonds, four solvent-bridged hydrogen bonds, three ion pairs, and numerous van der Waals interactions <ref name=ding />.
===Conformational changes===
Conformational changes upon the binding of OspA and LA-2 show that LA-2 recognition of OspA involves an induced fit mechanism where loops 1-3 conformations shift to optimize complementarity to the antigen-combining site <ref name=ding />. The overall structure of the C-terminal of OspA is unchanged upon the binding of LA-2 with comparison to the free OspA, except for the minor shift to accommodate for the binding. The maximum atomic shift is 4.7A at the site of Ser206.<ref>PMID: 11183781</ref>

<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

References: {{reflist}}

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-30T01:46:25Z

Safa Abdelhakim:

==Introduction==
===''Borrelia burgdoferi''===

The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/ Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to certain forms of complement-dependent immune response by the evasion of the [http://en.wikipedia.org/wiki/Alternative_complement_pathway alternative complement pathway] and the blocking of complement [http://en.wikipedia.org/wiki/Complement_component_3 C3]. <ref>PMID:18080415</ref> This resistance increases the importance of the complement independent immune response when combating ''B. burgdorferi''. Certain fragment antigen binding regions ([http://en.wikipedia.org/wiki/Fragment_antigen-binding fab]) of IgG and IgM monoclonal antibodies are bactericidal even in the absence of complement. Binding of these fabs to their corresponding outer surface protein (OspA and OspB) of ''B. burgdoferi'' leads to the lysis of the bacteria.<ref>PMID:15864264</ref>

===Fragment Antigen Binding (fab) Reigon===
[[Image:Fab reigon.png|right|thumb|Digestion of an antibody by Papain separates the fab reigons from the antibody]]
Fab consists of a heavy and a light chain and each chain is composed of a variable and a constant region. The [http://en.wikipedia.org/wiki/Paratope paratope] is located in the N terminal of the variable region of the [http://en.wikipedia.org/wiki/Immunoglobulin_heavy_chain heavy chain] and [http://en.wikipedia.org/wiki/Immunoglobulin_light_chain light chain] of the fab. The complement-independent fab regions that interact with these outer surface proteins are LA-2, which targets the C-terminal of OspA, and CB2 and H6831, which target the C-terminal of OspB. <ref>PMID:107164</ref>

==OspB and H6831==
<Structure load='1RJL' size='400' frame='true' align='right' caption='OspB and H6831 Fab complex' scene='Studio:G1SecL01/1/10' />

===Complex Interaction between OspB and H6831===
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

The <scene name='Studio:G1SecL01/1/10'>OspB-H6831 complex</scene> consist of two main components, the outer surface protein <scene name='Studio:G1SecL01/1/11'>OspB</scene>, and the <scene name='Studio:G1SecL01/1/12'>fab</scene>, subdivided into the <scene name='Studio:G1SecL01/1/14'>heavy chain</scene> and the <scene name='Studio:G1SecL01/1/13'>light chain</scene>. Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the <scene name='Studio:G1SecL01/1/15'>three adjacent surface-exposed loops</scene> at the C-terminal of OspB and some <scene name='Studio:G1SecL01/1/16'>residues</scene> on the fab heavy chain that include tyrosine, tryptophan, glutamate, and histidine.

The majority of the electrostatic and hydrogen-bonded interactions are between loop 2 (residues 250-254) and the fab heavy chain. <scene name='Studio:G1SecL01/1/17'>Lysine 253</scene> in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine (green link) and tryptophan (green link). It also makes hydrogen bonds with the glutamate (green link) in the heavy chain of the fab and forms an ionic bond. Carbonyl in loop 1 (green link) of the OspB interacts with histidine in the fab heavy chain. <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> of OspB interacts with fab light chain. <ref name=becker>PMID:15713683</ref>.

===Conformational Changes to OspB===
The binding leads to some conformational changes in OspB. Whereas Ding et al.<ref name=ding>PMID:11183781</ref> found no changes in the C-terminal of OspA upon the binding to the fab. The most significant difference between the free and the complexed structure of OspB is the loss of the central <scene name='Studio:G1SecL01/1/19'>beta sheet</scene> strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the Fab-binding site (residues 218 –220). In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts <ref name=becker />.

====Requirements for the Bactericidal Effect and Proposed Mechanism====
The fab binding destabilizes the [http://en.wikipedia.org/wiki/Bacterial_outer_membrane outer membrane] (OM) of B. burdorferi, with subsequent formation of [http://en.wikipedia.org/wiki/Spheroplast spheroplasts]. It has been observed that the bactericidal action, but not the binding, requires the presence of bivalent cations (Mg2+ and Ca2+). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the bivalent cations. It was speculated that OspB- Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>Escudero; Halluska et al. 1997</ref>.
Need to be rephrased and squeezed and may be a sentence about the cholestrol needs to be added and if there is a specific function for the charge triad it may be added

==OspA and LA-2==
<Structure load='1FJ1' size='400' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />
===OspA===
OspA is 53% similar to OspB. OspA is usually undetectable in the early stages of lyme disease, because it is down regulated when OspC is expressed (provide citation). Despite the similarity between OspA and OspB, both in vivo and vitro OspB is susceptible to cleavage by exogenous [http://en.wikipedia.org/wiki/Protease proteases], whereas OspA is relatively resistant (Becker, structural). This characteristic may have contributed to OspA being a better vaccine to lyme disease that is used to prevent transmission of B.burgodorferi from tick vector to mammalian host by complement-independent killing.<ref name=ding />
===Interaction between OspA and LA-2===
LA-2 is an IgM murine monoclonal antibody that interacts with three exposed loop on the C-terminal of OspA. These interactions include eight direct hydrogen bonds, four solvent-bridged hydrogen bonds, three ion pairs, and numerous van der Waals interactions <ref name=ding />.
===Conformational changes===
Conformational changes upon the binding of OspA and LA-2 show that LA-2 recognition of OspA involves an induced fit mechanism where loops 1-3 conformations shift to optimize complementarity to the antigen-combining site <ref name=ding />. The overall structure of the C-terminal of OspA is unchanged upon the binding of LA-2 with comparison to the free OspA, except for the minor shift to accommodate for the binding. The maximum atomic shift is 4.7A at the site of Ser206

<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

References: {{reflist}}

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-30T01:32:13Z

Safa Abdelhakim:

==Introduction==
===''Borrelia burgdoferi''===

The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/ Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to certain forms of complement-dependent immune response by the evasion of the [http://en.wikipedia.org/wiki/Alternative_complement_pathway alternative complement pathway] and the blocking of complement [http://en.wikipedia.org/wiki/Complement_component_3 C3]. <ref>PMID:18080415</ref> This resistance increases the importance of the complement independent immune response when combating ''B. burgdorferi''. Certain fragment antigen binding regions ([http://en.wikipedia.org/wiki/Fragment_antigen-binding fab]) of IgG and IgM monoclonal antibodies are bactericidal even in the absence of complement. Binding of these fabs to their corresponding outer surface protein (OspA and OspB) of ''B. burgdoferi'' leads to lysis of the bacteria.<ref>PMID:15864264</ref>

===Fragment Antigen Binding (fab) Reigon===
[[Image:Fab reigon.png|right|thumb|Digestion of an antibody by Papain separates the fab reigons from the antibody]]
There are two fab reigons per antibody, each composed of a variable and constant reigon. The variable region contains the [http://en.wikipedia.org/wiki/Paratope paratope], which recognizes the [http://en.wikipedia.org/wiki/Antigen antigen] [http://en.wikipedia.org/wiki/Epitope epitope], located at the N terminus of both the [http://en.wikipedia.org/wiki/Immunoglobulin_heavy_chain heavy chain] and [http://en.wikipedia.org/wiki/Immunoglobulin_light_chain light chain] of the fab. The complement-independent fab regions that interact with these outer surface proteins are LA-2, which targets the C-terminal of OspA, and CB2 and H6831, which target the C-terminal of OspB. <ref>PMID:107164</ref>

==OspB and H6831==
<Structure load='1RJL' size='400' frame='true' align='right' caption='OspB and H6831 Fab complex' scene='Studio:G1SecL01/1/10' />

===Complex Interaction between OspB and H6831===
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

The <scene name='Studio:G1SecL01/1/10'>OspB-H6831 complex</scene> consist of two main components, the outer surface protein <scene name='Studio:G1SecL01/1/11'>OspB</scene>, and the <scene name='Studio:G1SecL01/1/12'>fab</scene>, subdivided into the <scene name='Studio:G1SecL01/1/14'>heavy chain</scene> and the <scene name='Studio:G1SecL01/1/13'>light chain</scene>. Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the <scene name='Studio:G1SecL01/1/15'>three adjacent surface-exposed loops</scene> at the C-terminal of OspB and some <scene name='Studio:G1SecL01/1/16'>residues</scene> on the fab heavy chain that include tyrosine, tryptophan, glutamate, and histidine.

The majority of the electrostatic and hydrogen-bonded interactions are between loop 2 (residues 250-254) and the fab heavy chain. <scene name='Studio:G1SecL01/1/17'>Lysine 253</scene> in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine (green link) and tryptophan (green link). It also makes hydrogen bonds with the glutamate (green link) in the heavy chain of the fab and forms an ionic bond. Carbonyl in loop 1 (green link) of the OspB interacts with histidine in the fab heavy chain. <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> of OspB interacts with fab light chain. <ref name=becker>PMID:15713683</ref>.

===Conformational Changes to OspB===
The binding leads to some conformational changes in OspB. Whereas Ding et al.<ref name=ding>PMID:11183781</ref> found no changes in the C-terminal of OspA upon the binding to the fab. The most significant difference between the free and the complexed structure of OspB is the loss of the central <scene name='Studio:G1SecL01/1/19'>beta sheet</scene> strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the Fab-binding site (residues 218 –220). In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts <ref name=becker />.

====Requirements for the Bactericidal Effect and Proposed Mechanism====
The fab binding destabilizes the [http://en.wikipedia.org/wiki/Bacterial_outer_membrane outer membrane] (OM) of B. burdorferi, with subsequent formation of [http://en.wikipedia.org/wiki/Spheroplast spheroplasts]. It has been observed that the bactericidal action, but not the binding, requires the presence of bivalent cations (Mg2+ and Ca2+). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the bivalent cations. It was speculated that OspB- Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>Escudero; Halluska et al. 1997</ref>.
Need to be rephrased and squeezed and may be a sentence about the cholestrol needs to be added and if there is a specific function for the charge triad it may be added

==OspA and LA-2==
<Structure load='1FJ1' size='400' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />
===OspA===
OspA is 53% similar to OspB. OspA is usually undetectable in the early stages of lyme disease, because it is down regulated when OspC is expressed (provide citation). Despite the similarity between OspA and OspB, both in vivo and vitro OspB is susceptible to cleavage by exogenous [http://en.wikipedia.org/wiki/Protease proteases], whereas OspA is relatively resistant (Becker, structural). This characteristic may have contributed to OspA being a better vaccine to lyme disease that is used to prevent transmission of B.burgodorferi from tick vector to mammalian host by complement-independent killing.<ref name=ding />
===Interaction between OspA and LA-2===
LA-2 is an IgM murine monoclonal antibody that interacts with three exposed loop on the C-terminal of OspA. These interactions include eight direct hydrogen bonds, four solvent-bridged hydrogen bonds, three ion pairs, and numerous van der Waals interactions <ref name=ding />.
===Conformational changes===
Conformational changes upon the binding of OspA and LA-2 show that LA-2 recognition of OspA involves an induced fit mechanism where loops 1-3 conformations shift to optimize complementarity to the antigen-combining site <ref name=ding />. The overall structure of the C-terminal of OspA is unchanged upon the binding of LA-2 with comparison to the free OspA, except for the minor shift to accommodate for the binding. The maximum atomic shift is 4.7A at the site of Ser206

<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

References: {{reflist}}

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-30T01:13:40Z

Safa Abdelhakim:

==Introduction==
===''Borrelia burgdoferi''===

The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/ Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to certain forms of complement-dependent immune response by the evasion of the [http://en.wikipedia.org/wiki/Alternative_complement_pathway alternative complement pathway] and the blocking of complement [http://en.wikipedia.org/wiki/Complement_component_3 C3]. <ref>PMID:18080415</ref> This resistance increases the importance of the complement independent immune response when combating ''B. burgdorferi''. The fragment antigen binding regions ([http://en.wikipedia.org/wiki/Fragment_antigen-binding fab]) of IgG and IgM monoclonal antibodies to OspA and OspB, outer surface proteins of ''B. burgdoferi'' leads to a complement-independent lysis of the bacteria.<ref>PMID:15864264</ref>

===Fragment Antigen Binding (fab) Reigon===
[[Image:Fab reigon.png|right|thumb|Digestion of an antibody by Papain separates the fab reigons from the antibody]]
There are two fab reigons per antibody, each composed of a variable and constant reigon. The variable region contains the [http://en.wikipedia.org/wiki/Paratope paratope], which recognizes the [http://en.wikipedia.org/wiki/Antigen antigen] [http://en.wikipedia.org/wiki/Epitope epitope], located at the N terminus of both the [http://en.wikipedia.org/wiki/Immunoglobulin_heavy_chain heavy chain] and [http://en.wikipedia.org/wiki/Immunoglobulin_light_chain light chain] of the fab. The complement-independent fab regions that interact with these outer surface proteins are LA-2, which targets the C-terminal of OspA, and CB2 and H6831, which target the C-terminal of OspB. <ref>PMID:107164</ref>

==OspB and H6831==
<Structure load='1RJL' size='400' frame='true' align='right' caption='OspB and H6831 Fab complex' scene='Studio:G1SecL01/1/10' />

===Complex Interaction between OspB and H6831===
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

The <scene name='Studio:G1SecL01/1/10'>OspB-H6831 complex</scene> consist of two main components, the outer surface protein <scene name='Studio:G1SecL01/1/11'>OspB</scene>, and the <scene name='Studio:G1SecL01/1/12'>fab</scene>, subdivided into the <scene name='Studio:G1SecL01/1/14'>heavy chain</scene> and the <scene name='Studio:G1SecL01/1/13'>light chain</scene>. Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the <scene name='Studio:G1SecL01/1/15'>three adjacent surface-exposed loops</scene> at the C-terminal of OspB and some <scene name='Studio:G1SecL01/1/16'>residues</scene> on the fab heavy chain that include tyrosine, tryptophan, glutamate, and histidine.

The majority of the electrostatic and hydrogen-bonded interactions are between loop 2 (residues 250-254) and the fab heavy chain. <scene name='Studio:G1SecL01/1/17'>Lysine 253</scene> in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine (green link) and tryptophan (green link). It also makes hydrogen bonds with the glutamate (green link) in the heavy chain of the fab and forms an ionic bond. Carbonyl in loop 1 (green link) of the OspB interacts with histidine in the fab heavy chain. <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> of OspB interacts with fab light chain. <ref name=becker>PMID:15713683</ref>.

===Conformational Changes to OspB===
The binding leads to some conformational changes in OspB. Whereas Ding et al.<ref name=ding>PMID:11183781</ref> found no changes in the C-terminal of OspA upon the binding to the fab. The most significant difference between the free and the complexed structure of OspB is the loss of the central <scene name='Studio:G1SecL01/1/19'>beta sheet</scene> strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the Fab-binding site (residues 218 –220). In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts <ref name=becker />.

====Requirements for the Bactericidal Effect and Proposed Mechanism====
The fab binding destabilizes the [http://en.wikipedia.org/wiki/Bacterial_outer_membrane outer membrane] (OM) of B. burdorferi, with subsequent formation of [http://en.wikipedia.org/wiki/Spheroplast spheroplasts]. It has been observed that the bactericidal action, but not the binding, requires the presence of bivalent cations (Mg2+ and Ca2+). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the bivalent cations. It was speculated that OspB- Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>Escudero; Halluska et al. 1997</ref>.
Need to be rephrased and squeezed and may be a sentence about the cholestrol needs to be added and if there is a specific function for the charge triad it may be added

==OspA and LA-2==
<Structure load='1FJ1' size='400' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />
===OspA===
OspA is 53% similar to OspB. OspA is usually undetectable in the early stages of lyme disease, because it is down regulated when OspC is expressed (provide citation). Despite the similarity between OspA and OspB, both in vivo and vitro OspB is susceptible to cleavage by exogenous [http://en.wikipedia.org/wiki/Protease proteases], whereas OspA is relatively resistant (Becker, structural). This characteristic may have contributed to OspA being a better vaccine to lyme disease that is used to prevent transmission of B.burgodorferi from tick vector to mammalian host by complement-independent killing.<ref name=ding />
===Interaction between OspA and LA-2===
LA-2 is an IgM murine monoclonal antibody that interacts with three exposed loop on the C-terminal of OspA. These interactions include eight direct hydrogen bonds, four solvent-bridged hydrogen bonds, three ion pairs, and numerous van der Waals interactions <ref name=ding />.
===Conformational changes===
Conformational changes upon the binding of OspA and LA-2 show that LA-2 recognition of OspA involves an induced fit mechanism where loops 1-3 conformations shift to optimize complementarity to the antigen-combining site <ref name=ding />. The overall structure of the C-terminal of OspA is unchanged upon the binding of LA-2 with comparison to the free OspA, except for the minor shift to accommodate for the binding. The maximum atomic shift is 4.7A at the site of Ser206

<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

References: {{reflist}}

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-30T01:10:29Z

Safa Abdelhakim:

==Introduction==
===''Borrelia burgdoferi''===

The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/ Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to certain forms of complement-dependent immune response by the evasion of the ''[http://en.wikipedia.org/wiki/Alternative_complement_pathway alternative complement pathway]'' and the blocking of complement [http://en.wikipedia.org/wiki/Complement_component_3 C3]. <ref>PMID:18080415</ref> This resistance increases the importance of the complement independent immune response when combating ''B. burgdorferi'' [http://en.wikipedia.org/wiki/In_vivo ''in vivo'']. The fragment antigen binding regions ([http://en.wikipedia.org/wiki/Fragment_antigen-binding fab]) of IgG and IgM monoclonal antibodies to OspA and OspB, outer surface proteins of ''B. burgdoferi'' leads to a complement-independent lysis of the bacteria.<ref>PMID:15864264</ref>

===Fragment Antigen Binding (fab) Reigon===
[[Image:Fab reigon.png|right|thumb|Digestion of an antibody by Papain separates the fab reigons from the antibody]]
There are two fab reigons per antibody, each composed of a variable and constant reigon. The variable region contains the [http://en.wikipedia.org/wiki/Paratope paratope], which recognizes the [http://en.wikipedia.org/wiki/Antigen antigen] [http://en.wikipedia.org/wiki/Epitope epitope], located at the N terminus of both the [http://en.wikipedia.org/wiki/Immunoglobulin_heavy_chain heavy chain] and [http://en.wikipedia.org/wiki/Immunoglobulin_light_chain light chain] of the fab. The complement-independent fab regions that interact with these outer surface proteins are LA-2, which targets the C-terminal of OspA, and CB2 and H6831, which target the C-terminal of OspB. <ref>PMID:107164</ref>

==OspB and H6831==
<Structure load='1RJL' size='400' frame='true' align='right' caption='OspB and H6831 Fab complex' scene='Studio:G1SecL01/1/10' />

===Complex Interaction between OspB and H6831===
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

The <scene name='Studio:G1SecL01/1/10'>OspB-H6831 complex</scene> consist of two main components, the outer surface protein <scene name='Studio:G1SecL01/1/11'>OspB</scene>, and the <scene name='Studio:G1SecL01/1/12'>fab</scene>, subdivided into the <scene name='Studio:G1SecL01/1/14'>heavy chain</scene> and the <scene name='Studio:G1SecL01/1/13'>light chain</scene>. Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the <scene name='Studio:G1SecL01/1/15'>three adjacent surface-exposed loops</scene> at the C-terminal of OspB and some <scene name='Studio:G1SecL01/1/16'>residues</scene> on the fab heavy chain that include tyrosine, tryptophan, glutamate, and histidine.

The majority of the electrostatic and hydrogen-bonded interactions are between loop 2 (residues 250-254) and the fab heavy chain. <scene name='Studio:G1SecL01/1/17'>Lysine 253</scene> in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine (green link) and tryptophan (green link). It also makes hydrogen bonds with the glutamate (green link) in the heavy chain of the fab and forms an ionic bond. Carbonyl in loop 1 (green link) of the OspB interacts with histidine in the fab heavy chain. <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> of OspB interacts with fab light chain. <ref name=becker>PMID:15713683</ref>.

===Conformational Changes to OspB===
The binding leads to some conformational changes in OspB. Whereas Ding et al.<ref name=ding>PMID:11183781</ref> found no changes in the C-terminal of OspA upon the binding to the fab. The most significant difference between the free and the complexed structure of OspB is the loss of the central <scene name='Studio:G1SecL01/1/19'>beta sheet</scene> strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the Fab-binding site (residues 218 –220). In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts <ref name=becker />.

====Requirements for the Bactericidal Effect and Proposed Mechanism====
The fab binding destabilizes the [http://en.wikipedia.org/wiki/Bacterial_outer_membrane outer membrane] (OM) of B. burdorferi, with subsequent formation of [http://en.wikipedia.org/wiki/Spheroplast spheroplasts]. It has been observed that the bactericidal action, but not the binding, requires the presence of bivalent cations (Mg2+ and Ca2+). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the bivalent cations. It was speculated that OspB- Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>Escudero; Halluska et al. 1997</ref>.
Need to be rephrased and squeezed and may be a sentence about the cholestrol needs to be added and if there is a specific function for the charge triad it may be added

==OspA and LA-2==
<Structure load='1FJ1' size='400' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />
===OspA===
OspA is 53% similar to OspB. OspA is usually undetectable in the early stages of lyme disease, because it is down regulated when OspC is expressed (provide citation). Despite the similarity between OspA and OspB, both in vivo and vitro OspB is susceptible to cleavage by exogenous [http://en.wikipedia.org/wiki/Protease proteases], whereas OspA is relatively resistant (Becker, structural). This characteristic may have contributed to OspA being a better vaccine to lyme disease that is used to prevent transmission of B.burgodorferi from tick vector to mammalian host by complement-independent killing.<ref name=ding />
===Interaction between OspA and LA-2===
LA-2 is an IgM murine monoclonal antibody that interacts with three exposed loop on the C-terminal of OspA. These interactions include eight direct hydrogen bonds, four solvent-bridged hydrogen bonds, three ion pairs, and numerous van der Waals interactions <ref name=ding />.
===Conformational changes===
Conformational changes upon the binding of OspA and LA-2 show that LA-2 recognition of OspA involves an induced fit mechanism where loops 1-3 conformations shift to optimize complementarity to the antigen-combining site <ref name=ding />. The overall structure of the C-terminal of OspA is unchanged upon the binding of LA-2 with comparison to the free OspA, except for the minor shift to accommodate for the binding. The maximum atomic shift is 4.7A at the site of Ser206

<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>

References: {{reflist}}

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-29T17:53:42Z

Safa Abdelhakim:

==Introduction==
===''Borrelia burgdoferi''===

The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/ Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to certain forms of complement-dependent immune response by the evasion of the alternative complement pathway, and the blocking of complement [http://en.wikipedia.org/wiki/Complement_component_3 C3]. <ref>PMID:18080415</ref> This resistance increases the importance of the complement independent immune response when combating ''B. burgdorferi'' [http://en.wikipedia.org/wiki/In_vivo ''in vivo'']. The fragment antigen binding regions ([http://en.wikipedia.org/wiki/Fragment_antigen-binding fab]) of IgG and IgM monoclonal antibodies to OspA and OspB, outer surface proteins of ''B. burgdoferi'' leads to a complement-independent lysis of the bacteria.<ref>PMID:15864264</ref>

===Fragment Antigen Binding (fab) Reigon===
[[Image:Fab reigon.png|right|thumb|Digestion of an antibody by Papain separates the fab reigons from the antibody]]
There are two fab reigons per antibody, each composed of a variable and constant reigon. The variable region contains the [http://en.wikipedia.org/wiki/Paratope paratope], which recognizes the [http://en.wikipedia.org/wiki/Antigen antigen] [http://en.wikipedia.org/wiki/Epitope epitope], located at the N terminus of both the [http://en.wikipedia.org/wiki/Immunoglobulin_heavy_chain heavy chain] and [http://en.wikipedia.org/wiki/Immunoglobulin_light_chain light chain] of the fab. The complement-independent fab regions that interact with these outer surface proteins are LA-2, which targets the C-terminal of OspA, and CB2 and H6831, which target the C-terminal of OspB. <ref>PMID:107164</ref>

==OspB and H6831==
<Structure load='1RJL' size='300' frame='true' align='right' caption='OspB and H6831 Fab complex' scene='Studio:G1SecL01/1/10' />
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>
===Complex Interaction between OspB and H6831===
Fab-Osp complexes, such as the OspB-H6831 complex, consist of two main components; the <scene name='Studio:G1SecL01/1/11'>outer surface protein</scene> (OspB in this case), and the <scene name='Studio:G1SecL01/1/12'>fab</scene>, which is subdivided into the <scene name='Studio:G1SecL01/1/14'>heavy chain</scene>, and the <scene name='Studio:G1SecL01/1/13'>light chain</scene>. Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the three adjacent surface-exposed <scene name='Studio:G1SecL01/1/15'>loops</scene> at the C-terminal of OspB and some <scene name='Studio:G1SecL01/1/16'>residues</scene> on the fab heavy chain that include tyrosine, tryptophan, glutamate, and histidine. The majority of the electrostatic and hydrogen-bonded interactions are between loop 2 (residues 250-254) and the fab heavy chain. <scene name='Studio:G1SecL01/1/17'>Lysine 253</scene> in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine (green link) and tryptophan (green link). It also makes hydrogen bonds with the glutamate (green link) in the heavy chain of the fab and forms an ionic bond. Carbonyl in loop 1 (green link) of the OspB interacts with histidine in the fab heavy chain. <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> of OspB interacts with fab light chain. <ref>Becker; Bunikis et al. 2004</ref>.

===Conformational Changes to OspB===
The binding leads to some conformational changes in OspB. Whereas Ding et al.<ref>Ding et al</ref> found no changes in the C-terminal of OspA upon the binding to the fab. The most significant difference between the free and the complexed structure of OspB is the loss of the central <scene name='Studio:G1SecL01/1/19'>beta sheet</scene> strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the Fab-binding site (residues 218 –220). In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts <ref>Becker; Bunikis et al. 2004</ref>

====Requirements for the Bactericidal Effect and Proposed Mechanism====
The fab binding destabilizes the outer membrane (OM) of B. burdorferi, with subsequent formation of spheroplasts. It has been observed that the bactericidal action, but not the binding, requires the presence of bivalent cations (Mg2+ and Ca2+). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the bivalent cations. It was speculated that OspB- Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>Escudero; Halluska et al. 1997</ref>.
Need to be rephrased and squeezed and may be a sentence about the cholestrol needs to be added and if there is a specific function for the charge triad it may be added

==OspA and LA-2==
<Structure load='1FJ1' size='300' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />
===OspA===
OspA is 53% similar to OspB. OspA is usually undetectable in the early stages of lyme disease, because it is down regulated when OspC is expressed (provide citation). Despite the similarity between OspA and OspB, both in vivo and vitro OspB is susceptible to cleavage by exogenous proteases, whereas OspA is relatively resistant (Becker, structural). This characteristic may have contributed to OspA being a better vaccine to lyme disease that is used to prevent transmission of B.burgodorferi from tick vector to mammalian host by complement-independent killing.
===Interaction between OspA and LA-2===
LA-2 is an IgM murine monoclonal antibody that interacts with three exposed loop on the C-terminal of OspA. These interactions include eight direct hydrogen bonds, four solvent-bridged hydrogen bonds, three ion pairs, and numerous van der Waals interactions (Ding 200).
===Conformational changes===
Conformational changes upon the binding of OspA and LA-2 show that LA-2 recognition of OspA involves an induced fit mechanism where loops 1-3 conformations shift to optimize complementarity to the antigen-combining site (Ding 2000). The overall structure of the C-terminal of OspA is unchanged upon the binding of LA-2 with comparison to the free OspA, except for the minor shift to accommodate for the binding. The maximum atomic shift is 4.7A at the site of Ser206

References: {{reflist}}

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-29T15:55:21Z

Safa Abdelhakim:

==Introduction==
===''Borrelia burgdoferi''===

The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/ Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to certain forms of complement-dependent immune response by the evasion of the alternative complement pathway, and the blocking of complement C3. <ref>PMID:18080415</ref> This resistance increases the importance of the complement independent immune response when combating ''B. burgdorferi'' ''in vivo''. The fragment antigen binding regions of IgG and IgM monoclonal antibodies to OspA and OspB, outer surface proteins of ''B. burgdoferi'' leads to a complement-independent lysis of the bacteria.<ref>PMID:15864264</ref>

===Fragment Antigen Binding (fab) Reigon===
[[Image:Fab reigon.png|right|thumb|Digestion of an antibody by Papain separates the fab reigons from the antibody]]
The fragment antigen binding reigons, also known as fab reigons, consist of the light and N-terminus of the heavy chain of antibodies. There are two fab reigons per antibody, and each fab is composed of both a variable and constant reigon. The variable reigon contains the paratope (which binds to an antigen's epitope), located at the N terminus of both the heavy and light chains of the fab. The complement-independent fab reigons most pertienent to Lyme disease are IgG antibody fabs CB2 and H6831, which target the C-terminal of OspB, and IgM LA2, which targets OspB in ''B. burgdoferi''.<ref>PMID:107164</ref>

==OspB and H6831==
<Structure load='1RJL' size='300' frame='true' align='right' caption='OspB and H6831 Fab complex' scene='Studio:G1SecL01/1/10' />
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>
===Complex Interaction between OspB and H6831===
Fab-Osp complexes, such as the OspB-H6831 complex, consist of two main components; the <scene name='Studio:G1SecL01/1/11'>Outer Surface Protein</scene> (OspB in this case), and the <scene name='Studio:G1SecL01/1/12'>fab</scene>, which is subdivided into the <scene name='Studio:G1SecL01/1/14'>heavy chain</scene>, and the <scene name='Studio:G1SecL01/1/13'>light chain</scene>. Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the three adjacent surface-exposed <scene name='Studio:G1SecL01/1/15'>loops</scene> at the C-terminal of OspB and some <scene name='Studio:G1SecL01/1/16'>residues</scene> on the fab heavy chain that include tyrosine, tryptophan, glutamate, and histidine. The majority of the electrostatic and hydrogen-bonded interactions are between loop 2 (residues 250-254) and the fab heavy chain. <scene name='Studio:G1SecL01/1/17'>Lysine 253</scene> in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine (green link) and tryptophan (green link). It also makes hydrogen bonds with the glutamate (green link) in the heavy chain of the fab. Carbonyl in loop 1 (green link) of the OspB interacts with histidine in the fab heavy chain. <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> of OspB interacts with fab light chain. <ref>Becker; Bunikis et al. 2004</ref>.

===Conformational Changes to OspB===
The binding leads to some conformational changes in OspB. Whereas Ding et al.<ref>Ding et al</ref> found no changes in the C-terminal of OspA upon the binding to the fab. The most significant difference between the free and the complexed structure of OspB is the loss of the central <scene name='Studio:G1SecL01/1/19'>beta sheet</scene> strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the Fab-binding site (residues 218 –220). In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts <ref>Becker; Bunikis et al. 2004</ref>

====Requirements for the Bactericidal Effect and Proposed Mechanism====
The fab binding destabilizes the outer membrane (OM) of B. burdorferi, with subsequent formation of spheroplasts. It has been observed that the bactericidal action, but not the binding, requires the presence of bivalent cations (Mg2+ and Ca2+). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the bivalent cations. It was speculated that OspB- Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>Escudero; Halluska et al. 1997</ref>.
Need to be rephrased and squeezed and may be a sentence about the cholestrol needs to be added and if there is a specific function for the charge triad it may be added

==OspA and LA-2==
<Structure load='1FJ1' size='300' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

==Temporary Stuff==

<scene name='Studio:G1SecL01/Complex_s/1'>original scene S</scene>

<scene name='Studio:G1SecL01/Loop_2_s/1'>Loop 2 S</scene>

<scene name='Studio:G1SecL01/Lys_253_s/1'>lys 253 S</scene>

IgG antibody fabs CB2 and <scene name='Studio:G1SecL01/1/9'>H6831</scene>are structurally similar and both target the C-terminal of <scene name='Studio:G1SecL01/1/2'>OspB</scene>. H6831 consists of a <scene name='Studio:G1SecL01/1/3'>light</scene> and a <scene name='Studio:G1SecL01/1/4'>heavy</scene> chain and each chain is composed of a variable and a constant domain. The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>Escudero; Halluska et al. 1997</ref>##

<scene name='Studio:G1SecL01/1/5'>three exposed loops</scene>

<scene name='Studio:G1SecL01/1/6'>Lysine 253</scene>

<scene name='Studio:G1SecL01/1/7'>Lysine 253 with crucial heavy chain amino acids</scene>

<scene name='Studio:G1SecL01/1/8'>B sheet that gets removed</scene>

References: {{reflist}}

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-29T15:52:25Z

Safa Abdelhakim:

==Introduction==
===''Borrelia burgdoferi''===

The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/ Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to certain forms of complement-dependent immune response by the evasion of the alternative complement pathway, and the blocking of complement C3. <ref>PMID:18080415</ref> important diverse role of antibody. This resistance increases the importance of the complement independent immune response when combating ''Borrelia burgdorferi'' ''in vivo''. The fragment antigen binding reigons of IgG and IgM monoclonal antibodies to outer surface proteins (Osp) A and B of ''B. burgdoferi'' leads to a complement-independent lysis of the bacteria.<ref>PMID:15864264</ref>

===Fragment Antigen Binding (fab) Reigon===
[[Image:Fab reigon.png|right|thumb|Digestion of an antibody by Papain separates the fab reigons from the antibody]]
The fragment antigen binding reigons, also known as fab reigons, consist of the light and N-terminus of the heavy chain of antibodies. There are two fab reigons per antibody, and each fab is composed of both a variable and constant reigon. The variable reigon contains the paratope (which binds to an antigen's epitope), located at the N terminus of both the heavy and light chains of the fab. The complement-independent fab reigons most pertienent to Lyme disease are IgG antibody fabs CB2 and H6831, which target the C-terminal of OspB, and IgM LA2, which targets OspB in ''B. burgdoferi''.<ref>PMID:107164</ref>

==OspB and H6831==
<Structure load='1RJL' size='300' frame='true' align='right' caption='OspB and H6831 Fab complex' scene='Studio:G1SecL01/1/10' />
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>
===Complex Interaction between OspB and H6831===
Fab-Osp complexes, such as the OspB-H6831 complex, consist of two main components; the <scene name='Studio:G1SecL01/1/11'>Outer Surface Protein</scene> (OspB in this case), and the <scene name='Studio:G1SecL01/1/12'>fab</scene>, which is subdivided into the <scene name='Studio:G1SecL01/1/14'>heavy chain</scene>, and the <scene name='Studio:G1SecL01/1/13'>light chain</scene>. Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the three adjacent surface-exposed <scene name='Studio:G1SecL01/1/15'>loops</scene> at the C-terminal of OspB and some <scene name='Studio:G1SecL01/1/16'>residues</scene> on the fab heavy chain that include tyrosine, tryptophan, glutamate, and histidine. The majority of the electrostatic and hydrogen-bonded interactions are between loop 2 (residues 250-254) and the fab heavy chain. <scene name='Studio:G1SecL01/1/17'>Lysine 253</scene> in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine (green link) and tryptophan (green link). It also makes hydrogen bonds with the glutamate (green link) in the heavy chain of the fab. Carbonyl in loop 1 (green link) of the OspB interacts with histidine in the fab heavy chain. <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> of OspB interacts with fab light chain. <ref>Becker; Bunikis et al. 2004</ref>.

===Conformational Changes to OspB===
The binding leads to some conformational changes in OspB. Whereas Ding et al.<ref>Ding et al</ref> found no changes in the C-terminal of OspA upon the binding to the fab. The most significant difference between the free and the complexed structure of OspB is the loss of the central <scene name='Studio:G1SecL01/1/19'>beta sheet</scene> strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the Fab-binding site (residues 218 –220). In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts <ref>Becker; Bunikis et al. 2004</ref>

====Requirements for the Bactericidal Effect and Proposed Mechanism====
The fab binding destabilizes the outer membrane (OM) of B. burdorferi, with subsequent formation of spheroplasts. It has been observed that the bactericidal action, but not the binding, requires the presence of bivalent cations (Mg2+ and Ca2+). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the bivalent cations. It was speculated that OspB- Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>Escudero; Halluska et al. 1997</ref>.
Need to be rephrased and squeezed and may be a sentence about the cholestrol needs to be added and if there is a specific function for the charge triad it may be added

==OspA and LA-2==
<Structure load='1FJ1' size='300' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

==Temporary Stuff==

<scene name='Studio:G1SecL01/Complex_s/1'>original scene S</scene>

<scene name='Studio:G1SecL01/Loop_2_s/1'>Loop 2 S</scene>

<scene name='Studio:G1SecL01/Lys_253_s/1'>lys 253 S</scene>

IgG antibody fabs CB2 and <scene name='Studio:G1SecL01/1/9'>H6831</scene>are structurally similar and both target the C-terminal of <scene name='Studio:G1SecL01/1/2'>OspB</scene>. H6831 consists of a <scene name='Studio:G1SecL01/1/3'>light</scene> and a <scene name='Studio:G1SecL01/1/4'>heavy</scene> chain and each chain is composed of a variable and a constant domain. The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>Escudero; Halluska et al. 1997</ref>##

<scene name='Studio:G1SecL01/1/5'>three exposed loops</scene>

<scene name='Studio:G1SecL01/1/6'>Lysine 253</scene>

<scene name='Studio:G1SecL01/1/7'>Lysine 253 with crucial heavy chain amino acids</scene>

<scene name='Studio:G1SecL01/1/8'>B sheet that gets removed</scene>

References: {{reflist}}

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-29T15:51:29Z

Safa Abdelhakim:

==Introduction==
===''Borrelia burgdoferi''===

The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/ Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to certain forms of complement-dependent immune response by the evasion of the alternative complement pathway, and the blocking of complement C3. <ref>PMID:18080415</ref> important diverse role of antibody. This resistance increases the importance of the complement independent immune response when combating ''Borrelia burgdorferi'' ''in vivo''. The fragment antigen binding reigons of IgG and IgM monoclonal antibodies to outer surface proteins (Osp) A and B of ''B. burgdoferi'' leads to a complement-independent lysis of the bacteria.<ref>PMID:15864264</ref>

===Fragment Antigen Binding (fab) Reigon===
[[Image:Fab reigon.png|right|thumb|Digestion of an antibody by Papain separates the fab reigons from the antibody]]
The fragment antigen binding reigons, also known as fab reigons, consist of the light and N-terminus of the heavy chain of antibodies. There are two fab reigons per antibody, and each fab is composed of both a variable and constant reigon. The variable reigon contains the paratope (which binds to an antigen's epitope), located at the N terminus of both the heavy and light chains of the fab. The complement-independent fab reigons most pertienent to Lyme disease are IgG antibody fabs CB2 and H6831, which target the C-terminal of OspB, and ????? IgG LA2, which targets OspB in ''B. burgdoferi''.<ref>PMID:107164</ref>

==OspB and H6831==
<Structure load='1RJL' size='300' frame='true' align='right' caption='OspB and H6831 Fab complex' scene='Studio:G1SecL01/1/10' />
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>
===Complex Interaction between OspB and H6831===
Fab-Osp complexes, such as the OspB-H6831 complex, consist of two main components; the <scene name='Studio:G1SecL01/1/11'>Outer Surface Protein</scene> (OspB in this case), and the <scene name='Studio:G1SecL01/1/12'>fab</scene>, which is subdivided into the <scene name='Studio:G1SecL01/1/14'>heavy chain</scene>, and the <scene name='Studio:G1SecL01/1/13'>light chain</scene>. Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the three adjacent surface-exposed <scene name='Studio:G1SecL01/1/15'>loops</scene> at the C-terminal of OspB and some <scene name='Studio:G1SecL01/1/16'>residues</scene> on the fab heavy chain that include tyrosine, tryptophan, glutamate, and histidine. The majority of the electrostatic and hydrogen-bonded interactions are between loop 2 (residues 250-254) and the fab heavy chain. <scene name='Studio:G1SecL01/1/17'>Lysine 253</scene> in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine (green link) and tryptophan (green link). It also makes hydrogen bonds with the glutamate (green link) in the heavy chain of the fab. Carbonyl in loop 1 (green link) of the OspB interacts with histidine in the fab heavy chain. <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> of OspB interacts with fab light chain. <ref>Becker; Bunikis et al. 2004</ref>.

===Conformational Changes to OspB===
The binding leads to some conformational changes in OspB. Whereas Ding et al.<ref>Ding et al</ref> found no changes in the C-terminal of OspA upon the binding to the fab. The most significant difference between the free and the complexed structure of OspB is the loss of the central <scene name='Studio:G1SecL01/1/19'>beta sheet</scene> strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the Fab-binding site (residues 218 –220). In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts <ref>Becker; Bunikis et al. 2004</ref>

====Requirements for the Bactericidal Effect and Proposed Mechanism====
The fab binding destabilizes the outer membrane (OM) of B. burdorferi, with subsequent formation of spheroplasts. It has been observed that the bactericidal action, but not the binding, requires the presence of bivalent cations (Mg2+ and Ca2+). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the bivalent cations. It was speculated that OspB- Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>Escudero; Halluska et al. 1997</ref>.
Need to be rephrased and squeezed and may be a sentence about the cholestrol needs to be added and if there is a specific function for the charge triad it may be added

==OspA and LA-2==
<Structure load='1FJ1' size='300' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

==Temporary Stuff==

<scene name='Studio:G1SecL01/Complex_s/1'>original scene S</scene>

<scene name='Studio:G1SecL01/Loop_2_s/1'>Loop 2 S</scene>

<scene name='Studio:G1SecL01/Lys_253_s/1'>lys 253 S</scene>

IgG antibody fabs CB2 and <scene name='Studio:G1SecL01/1/9'>H6831</scene>are structurally similar and both target the C-terminal of <scene name='Studio:G1SecL01/1/2'>OspB</scene>. H6831 consists of a <scene name='Studio:G1SecL01/1/3'>light</scene> and a <scene name='Studio:G1SecL01/1/4'>heavy</scene> chain and each chain is composed of a variable and a constant domain. The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>Escudero; Halluska et al. 1997</ref>##

<scene name='Studio:G1SecL01/1/5'>three exposed loops</scene>

<scene name='Studio:G1SecL01/1/6'>Lysine 253</scene>

<scene name='Studio:G1SecL01/1/7'>Lysine 253 with crucial heavy chain amino acids</scene>

<scene name='Studio:G1SecL01/1/8'>B sheet that gets removed</scene>

References: {{reflist}}

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-29T15:46:46Z

Safa Abdelhakim:

==Introduction==
===''Borrelia burgdoferi''===

The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/ Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to certain forms of complement-dependent immune response by the evasion of the alternative complement pathway, and the blocking of complement C3. <ref>18080415</ref> important diverse role of antibody. This resistance increases the importance of the complement independent immune response when combating ''Borrelia burgdorferi'' ''in vivo''. The fragment antigen binding reigons of IgG and IgM monoclonal antibodies to outer surface proteins (Osp) A and B of ''B. burgdoferi'' leads to a complement-independent lysis of the bacteria.<ref>PMID:15864264</ref>

===Fragment Antigen Binding (fab) Reigon===
[[Image:Fab reigon.png|right|thumb|Digestion of an antibody by Papain separates the fab reigons from the antibody]]
The fragment antigen binding reigons, also known as fab reigons, consist of the light and N-terminus of the heavy chain of antibodies. There are two fab reigons per antibody, and each fab is composed of both a variable and constant reigon. The variable reigon contains the paratope (which binds to an antigen's epitope), located at the N terminus of both the heavy and light chains of the fab. The complement-independent fab reigons most pertienent to Lyme disease are IgG antibody fabs CB2 and H6831, which target the C-terminal of OspB, and ????? IgG LA2, which targets OspB in ''B. burgdoferi'' <ref>Putnam 1979</ref>.

==OspB and H6831==
<Structure load='1RJL' size='300' frame='true' align='right' caption='OspB and H6831 Fab complex' scene='Studio:G1SecL01/1/10' />
<scene name='Studio:G1SecL01/1/10'>Restore Original Scene</scene>
===Complex Interaction between OspB and H6831===
Fab-Osp complexes, such as the OspB-H6831 complex, consist of two main components; the <scene name='Studio:G1SecL01/1/11'>Outer Surface Protein</scene> (OspB in this case), and the <scene name='Studio:G1SecL01/1/12'>fab</scene>, which is subdivided into the <scene name='Studio:G1SecL01/1/14'>heavy chain</scene>, and the <scene name='Studio:G1SecL01/1/13'>light chain</scene>. Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the three adjacent surface-exposed <scene name='Studio:G1SecL01/1/15'>loops</scene> at the C-terminal of OspB and some <scene name='Studio:G1SecL01/1/16'>residues</scene> on the fab heavy chain that include tyrosine, tryptophan, glutamate, and histidine. The majority of the electrostatic and hydrogen-bonded interactions are between loop 2 (residues 250-254) and the fab heavy chain. <scene name='Studio:G1SecL01/1/17'>Lysine 253</scene> in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine (green link) and tryptophan (green link). It also makes hydrogen bonds with the glutamate (green link) in the heavy chain of the fab. Carbonyl in loop 1 (green link) of the OspB interacts with histidine in the fab heavy chain. <scene name='Studio:G1SecL01/1/18'>Loop 3</scene> of OspB interacts with fab light chain. <ref>Becker; Bunikis et al. 2004</ref>.

===Conformational Changes to OspB===
The binding leads to some conformational changes in OspB. Whereas Ding et al.<ref>Ding et al</ref> found no changes in the C-terminal of OspA upon the binding to the fab. The most significant difference between the free and the complexed structure of OspB is the loss of the central <scene name='Studio:G1SecL01/1/19'>beta sheet</scene> strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the Fab-binding site (residues 218 –220). In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts <ref>Becker; Bunikis et al. 2004</ref>

====Requirements for the Bactericidal Effect and Proposed Mechanism====
The fab binding destabilizes the outer membrane (OM) of B. burdorferi, with subsequent formation of spheroplasts. It has been observed that the bactericidal action, but not the binding, requires the presence of bivalent cations (Mg2+ and Ca2+). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the bivalent cations. It was speculated that OspB- Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>Escudero; Halluska et al. 1997</ref>.
Need to be rephrased and squeezed and may be a sentence about the cholestrol needs to be added and if there is a specific function for the charge triad it may be added

==OspA and LA-2==
<Structure load='1FJ1' size='300' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

==Temporary Stuff==

<scene name='Studio:G1SecL01/Complex_s/1'>original scene S</scene>

<scene name='Studio:G1SecL01/Loop_2_s/1'>Loop 2 S</scene>

<scene name='Studio:G1SecL01/Lys_253_s/1'>lys 253 S</scene>

IgG antibody fabs CB2 and <scene name='Studio:G1SecL01/1/9'>H6831</scene>are structurally similar and both target the C-terminal of <scene name='Studio:G1SecL01/1/2'>OspB</scene>. H6831 consists of a <scene name='Studio:G1SecL01/1/3'>light</scene> and a <scene name='Studio:G1SecL01/1/4'>heavy</scene> chain and each chain is composed of a variable and a constant domain. The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>Escudero; Halluska et al. 1997</ref>##

<scene name='Studio:G1SecL01/1/5'>three exposed loops</scene>

<scene name='Studio:G1SecL01/1/6'>Lysine 253</scene>

<scene name='Studio:G1SecL01/1/7'>Lysine 253 with crucial heavy chain amino acids</scene>

<scene name='Studio:G1SecL01/1/8'>B sheet that gets removed</scene>

References: {{reflist}}

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-27T22:40:00Z

Safa Abdelhakim:

==Introduction==
A causative agent of lyme disease is Borrelia burgdorferi, a gram negative, helically coiled bacteria that belongs to spirochete phylum. Antibody (blue link and a picture) play a versatile and important role in fighting the Borrelia. The borrelia develops resistance to certain forms of complement-dependent killing, by the evasion of the alternative complement pathway and blocking C3. (La Rocca and Benach 2008) important diverse role of antibody. This increases the importance of the Complement independent killing in fighting the Borrelia burgdorferi. Certain Fragment Antigen Binding fragments of antibody are bactericidal even in the absence of a complement. The binding of specific fabs of IgG and IgM monoclonal antibodies to OspA and OspB of the borrelia leads to a complement-independent lysis of the bacteria (Connolly and Benach 2005).

====Fragment Antigen Binding (fab)====
IgG antibody fabs CB2 and H6831(green link), which are structurally similar, target the C-terminal of OspB (green link). H6831 consists of a heavy (green link) and a light (green link) chain and each chain is composed of a variable and a constant domain. The paratope (binding site to the antigen) is located in the N terminal of the variable region of both the heavy and the light chains (Putnam 1979).

====Interaction between OspB and H6831====
Complex interaction between OspB and H6831(Green link)
Most hydrogen bonds and electrostatic interactions that are responsible for the binding of H6831 to OspB are between the three adjacent surface-exposed loops (Green link) at the C-terminal of OspB and some residues on the fab heavy chain (Green link) that include tyrosine, tryptophan, glutamate, and histidine. The majority of the electrostatic and hydrogen-bonded interactions are between loop 2 (residues 250-254) and the fab heavy chain. Lysine 253 (green link) in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine (green link) and tryptophan (green link). It also makes hydrogen bonds with the glutamate (green link) in the heavy chain of the fab. Carbonyl in loop 1 (green link) of the OspB interacts with histidine in the fab heavy chain. Loop 3 (green link) of OspB interacts with fab light chain. (Becker; Bunikis et al. 2004).

====Conformational Changes to OspB====
The binding leads to some conformational changes in OspB. Whereas Ding et al. found no changes in the C-terminal of OspA upon the binding to the fab. The most significant difference between the free and the complexed structure of OspB is the loss of the central beta sheet strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the Fab-binding site (residues 218 –220). In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts (Becker; Bunikis et al. 2004)

====Requirements for the bactericidal effect and proposed mechanism====
The fab binding destabilizes the outer membrane (OM) of B. burdorferi, with subsequent formation of spheroplasts. It has been observed that the bactericidal action, but not the binding, requires the presence of bivalent cations (Mg2+ and Ca2+). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the bivalent cations. It was speculated that OspB- Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997).
Need to be rephrased and squeezed and may be a sentence about the cholestrol needs to be added and if there is a specific function for the charge triad it may be added

====OspA and LA-2====

<scene name='Studio:G1SecL01/Complex_s/1'>original scene S</scene>

<scene name='Studio:G1SecL01/Loop_2_s/1'>Loop 2 S</scene>

<scene name='Studio:G1SecL01/Lys_253_s/1'>lys 253 S</scene>

<Structure load='1RJL' size='300' frame='true' align='right' caption='OspB and H6831 Fab complex' scene='Studio:G1SecL01/Alabeled/2' />
<scene name='Studio:G1SecL01/1/1'>Restore Original Scene</scene>

IgG antibody fabs CB2 and <scene name='Studio:G1SecL01/1/9'>H6831</scene>are structurally similar and both target the C-terminal of <scene name='Studio:G1SecL01/1/2'>OspB</scene>. H6831 consists of a <scene name='Studio:G1SecL01/1/3'>light</scene> and a <scene name='Studio:G1SecL01/1/4'>heavy</scene> chain and each chain is composed of a variable and a constant domain. The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)##

<scene name='Studio:G1SecL01/1/5'>three exposed loops</scene>

<scene name='Studio:G1SecL01/1/6'>Lysine 253</scene>

<scene name='Studio:G1SecL01/1/7'>Lysine 253 with crucial heavy chain amino acids</scene>

<scene name='Studio:G1SecL01/1/8'>B sheet that gets removed</scene>

<Structure load='1FJ1' size='300' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-27T03:38:25Z

Safa Abdelhakim:

==Introduction==
===Lyme Disease===
The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease|Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi| Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete| spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/| Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to complement-dependent lysis. Lysis in the absence of complement is necessary to clear ''Borrelia burgdorferi''.
===Complement Independent Antibodies===
Monoclonal Antibodies IgG and IgM are complement independent antibodies, and are not dependent on a specific complement in order to successfully bind.

====Fragment Antigen Binding Reigons====
The key to the bacteriacidal properties of these antibodies are the Fragment Antigen Binding (or fab) reigons of the antibody, which consists of the light chain and N-Terminus of the heavy chain in of the antibody.
[[Image:Fab reigon.png|thumb|right|Digestion of an Antibody by Paipin clearly shows two Fab reigons present on each antibody]]
The binding of specific fabs of IgG and IgM monoclonal antibodies to OspA and OspB of the ''Borrelia'' leads to a complement-independent lysis of the bacteria. <ref>PMID:15864264</ref>

==Interaction With OspB==

<scene name='Studio:G1SecL01/Complex_s/1'>original scene S</scene>

<scene name='Studio:G1SecL01/Loop_2_s/1'>Loop 2 S</scene>

<scene name='Studio:G1SecL01/Lys_253_s/1'>lys 253 S</scene>

<Structure load='1RJL' size='300' frame='true' align='right' caption='OspB and H6831 Fab complex' scene='Studio:G1SecL01/Alabeled/2' />
<scene name='Studio:G1SecL01/1/1'>Restore Original Scene</scene>
===OspB + H6831===

IgG antibody fabs CB2 and <scene name='Studio:G1SecL01/1/9'>H6831</scene>are structurally similar and both target the C-terminal of <scene name='Studio:G1SecL01/1/2'>OspB</scene>. H6831 consists of a <scene name='Studio:G1SecL01/1/3'>light</scene> and a <scene name='Studio:G1SecL01/1/4'>heavy</scene> chain and each chain is composed of a variable and a constant domain. The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)##

===Lys-253===

<scene name='Studio:G1SecL01/1/5'>three exposed loops</scene>

<scene name='Studio:G1SecL01/1/6'>Lysine 253</scene>

<scene name='Studio:G1SecL01/1/7'>Lysine 253 with crucial heavy chain amino acids</scene>

<scene name='Studio:G1SecL01/1/8'>B sheet that gets removed</scene>

==Homologous Structures in OspA===

<Structure load='1FJ1' size='300' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

IgG antibody fabs CB2 and H6831, which are structurally similar, target the C-terminal of OspB. H6831 consists of a heavy and a light chain and each chain is composed of a variable and a constant domain. The paratope (binding site to the antigen) is located in the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). The fab binding destabilizes the outer membrane (OM) of B. burdorferi, with subsequent formation of spheroplasts. It has been observed that the bactericidal action, but not the binding, requires the presence of bivalent cations (Mg2+ and Ca2+). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the bivalent cations. It was speculated that OspB- Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)
Most interactions between H6831 and OspB are between the three adjacent surface-exposed loops at the C-terminal of OspB and some residues on the fab heavy chain that include tyrosine, tryptophan, glutamate, and histidine. The majority of the electrostatic and hydrogen-bonded interactions are between loop 2 (residues 250-254) and the fab heavy chain. Lysine 253 in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine and tryptophan. It also makes hydrogen bonds with the glutamate in the heavy chain of the fab. Additional interactions were observed between the carbonyl in loop 1 of the OspB and the histidine in the fab heavy chain and between loop 3 of OspB and fab light chain. (Becker; Bunikis et al. 2004).
Whereas Ding et al. found no changes in the C-terminal of OspA upon the binding to the fab, Becker et al. study using crystallography has showed structural changes in OspB upon binding. The most significant difference between the free and the complexed structure of OspB is the loss of the central beta sheet strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the Fab-binding site (residues 218 –220). In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts (Becker; Bunikis et al. 2004)

OspB PDB: 1P4B

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-27T03:35:02Z

Safa Abdelhakim:

==Introduction==
===Lyme Disease===
The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease|Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi| Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete| spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/| Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to complement-dependent lysis. Lysis in the absence of complement is necessary to clear ''Borrelia burgdorferi''.
===Complement Independent Antibodies===
Monoclonal Antibodies IgG and IgM are complement independent antibodies, and are not dependent on a specific complement in order to successfully bind.

====Fragment Antigen Binding Reigons====
The key to the bacteriacidal properties of these antibodies are the Fragment Antigen Binding (or fab) reigons of the antibody, which consists of the light chain and N-Terminus of the heavy chain in of the antibody.
[[Image:Fab reigon.png|thumb|right|Digestion of an Antibody by Paipin clearly shows two Fab reigons present on each antibody]]
The binding of specific fabs of IgG and IgM monoclonal antibodies to OspA and OspB of the ''Borrelia'' leads to a complement-independent lysis of the bacteria. <ref>PMID:15864264</ref>

==Interaction With OspB==

<scene name='Studio:G1SecL01/Complex_s/1'>original scene S</scene>

<scene name='Studio:G1SecL01/Loop_2_s/1'>Loop 2 S</scene>

<Structure load='1RJL' size='300' frame='true' align='right' caption='OspB and H6831 Fab complex' scene='Studio:G1SecL01/Alabeled/2' />
<scene name='Studio:G1SecL01/1/1'>Restore Original Scene</scene>
===OspB + H6831===

IgG antibody fabs CB2 and <scene name='Studio:G1SecL01/1/9'>H6831</scene>are structurally similar and both target the C-terminal of <scene name='Studio:G1SecL01/1/2'>OspB</scene>. H6831 consists of a <scene name='Studio:G1SecL01/1/3'>light</scene> and a <scene name='Studio:G1SecL01/1/4'>heavy</scene> chain and each chain is composed of a variable and a constant domain. The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)##

===Lys-253===

<scene name='Studio:G1SecL01/1/5'>three exposed loops</scene>

<scene name='Studio:G1SecL01/1/6'>Lysine 253</scene>

<scene name='Studio:G1SecL01/1/7'>Lysine 253 with crucial heavy chain amino acids</scene>

<scene name='Studio:G1SecL01/1/8'>B sheet that gets removed</scene>

==Homologous Structures in OspA===

<Structure load='1FJ1' size='300' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

IgG antibody fabs CB2 and H6831, which are structurally similar, target the C-terminal of OspB. H6831 consists of a heavy and a light chain and each chain is composed of a variable and a constant domain. The paratope (binding site to the antigen) is located in the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). The fab binding destabilizes the outer membrane (OM) of B. burdorferi, with subsequent formation of spheroplasts. It has been observed that the bactericidal action, but not the binding, requires the presence of bivalent cations (Mg2+ and Ca2+). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the bivalent cations. It was speculated that OspB- Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)
Most interactions between H6831 and OspB are between the three adjacent surface-exposed loops at the C-terminal of OspB and some residues on the fab heavy chain that include tyrosine, tryptophan, glutamate, and histidine. The majority of the electrostatic and hydrogen-bonded interactions are between loop 2 (residues 250-254) and the fab heavy chain. Lysine 253 in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine and tryptophan. It also makes hydrogen bonds with the glutamate in the heavy chain of the fab. Additional interactions were observed between the carbonyl in loop 1 of the OspB and the histidine in the fab heavy chain and between loop 3 of OspB and fab light chain. (Becker; Bunikis et al. 2004).
Whereas Ding et al. found no changes in the C-terminal of OspA upon the binding to the fab, Becker et al. study using crystallography has showed structural changes in OspB upon binding. The most significant difference between the free and the complexed structure of OspB is the loss of the central beta sheet strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the Fab-binding site (residues 218 –220). In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts (Becker; Bunikis et al. 2004)

OspB PDB: 1P4B

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-27T03:31:15Z

Safa Abdelhakim:

==Introduction==
===Lyme Disease===
The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease|Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi| Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete| spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/| Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to complement-dependent lysis. Lysis in the absence of complement is necessary to clear ''Borrelia burgdorferi''.
===Complement Independent Antibodies===
Monoclonal Antibodies IgG and IgM are complement independent antibodies, and are not dependent on a specific complement in order to successfully bind.

====Fragment Antigen Binding Reigons====
The key to the bacteriacidal properties of these antibodies are the Fragment Antigen Binding (or fab) reigons of the antibody, which consists of the light chain and N-Terminus of the heavy chain in of the antibody.
[[Image:Fab reigon.png|thumb|right|Digestion of an Antibody by Paipin clearly shows two Fab reigons present on each antibody]]
The binding of specific fabs of IgG and IgM monoclonal antibodies to OspA and OspB of the ''Borrelia'' leads to a complement-independent lysis of the bacteria. <ref>PMID:15864264</ref>

==Interaction With OspB==

<scene name='Studio:G1SecL01/Complex_s/1'>original scene S</scene>

<Structure load='1RJL' size='300' frame='true' align='right' caption='OspB and H6831 Fab complex' scene='Studio:G1SecL01/Alabeled/2' />
<scene name='Studio:G1SecL01/1/1'>Restore Original Scene</scene>
===OspB + H6831===

IgG antibody fabs CB2 and <scene name='Studio:G1SecL01/1/9'>H6831</scene>are structurally similar and both target the C-terminal of <scene name='Studio:G1SecL01/1/2'>OspB</scene>. H6831 consists of a <scene name='Studio:G1SecL01/1/3'>light</scene> and a <scene name='Studio:G1SecL01/1/4'>heavy</scene> chain and each chain is composed of a variable and a constant domain. The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)##

===Lys-253===

<scene name='Studio:G1SecL01/1/5'>three exposed loops</scene>

<scene name='Studio:G1SecL01/1/6'>Lysine 253</scene>

<scene name='Studio:G1SecL01/1/7'>Lysine 253 with crucial heavy chain amino acids</scene>

<scene name='Studio:G1SecL01/1/8'>B sheet that gets removed</scene>

==Homologous Structures in OspA===

<Structure load='1FJ1' size='300' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

IgG antibody fabs CB2 and H6831, which are structurally similar, target the C-terminal of OspB. H6831 consists of a heavy and a light chain and each chain is composed of a variable and a constant domain. The paratope (binding site to the antigen) is located in the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). The fab binding destabilizes the outer membrane (OM) of B. burdorferi, with subsequent formation of spheroplasts. It has been observed that the bactericidal action, but not the binding, requires the presence of bivalent cations (Mg2+ and Ca2+). Escudero et al. study demonstrated the inability of fab to kill bacteria in the absence of the bivalent cations. It was speculated that OspB- Cb2 (a fab similar to H6831) complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)
Most interactions between H6831 and OspB are between the three adjacent surface-exposed loops at the C-terminal of OspB and some residues on the fab heavy chain that include tyrosine, tryptophan, glutamate, and histidine. The majority of the electrostatic and hydrogen-bonded interactions are between loop 2 (residues 250-254) and the fab heavy chain. Lysine 253 in loop 2 of OspB has a necessary and major role due to its central position in the exposed loops. A mutation at its position abrogates the binding interaction and causes the resistance of the bacteria to the bactericidal effect of the fab. Lys 253 binds to the two aromatic residues on the fab heavy chain, tyrosine and tryptophan. It also makes hydrogen bonds with the glutamate in the heavy chain of the fab. Additional interactions were observed between the carbonyl in loop 1 of the OspB and the histidine in the fab heavy chain and between loop 3 of OspB and fab light chain. (Becker; Bunikis et al. 2004).
Whereas Ding et al. found no changes in the C-terminal of OspA upon the binding to the fab, Becker et al. study using crystallography has showed structural changes in OspB upon binding. The most significant difference between the free and the complexed structure of OspB is the loss of the central beta sheet strands 1-4. Both small positional shifts near the Fab binding site and a few larger structural changes away from the binding site were observed. The largest shifts (7– 8 Å) correspond to the repositioning of a loop opposite the Fab-binding site (residues 218 –220). In the free OspB structure, all regions that exhibit shifts are adjacent to the central sheet; in the OspB-H6831 complex they all shift toward, and slightly overlap, the position of the missing sheet. These observations suggest that the larger conformational changes are related to the loss of the central sheet, which could have happened through proteolytic cleavage or fortuitous crystal contacts (Becker; Bunikis et al. 2004)

OspB PDB: 1P4B

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-25T05:24:23Z

Safa Abdelhakim:

==Introduction==
The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease|Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi| Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete| spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/| Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to complement-dependent lysis. Lysis in the absence of complement is necessary to clear ''Borrelia burgdorferi''. Certain Fragment Antigen Binding (fab) fragments of antibody are bactericidal even in the absence of a complement. The binding of specific fabs of IgG and IgM monoclonal antibodies to OspA and OspB of the ''Borrelia'' leads to a complement-independent lysis of the bacteria. <ref>PMID:15864264</ref>

<Structure load='1RJL' size='300' frame='true' align='right' caption='OspB_H6831' scene='Studio:G1SecL01/Ospb_h6831_complex/2' />

==Interaction With OspB==
===OspB + H6831===

<scene name='Studio:G1SecL01/Ospb_h6831_complex/2'>Restore original scene</scene>

<scene name='Studio:G1SecL01/Ospb/2'>OspB</scene>

IgG antibody fabs CB2 and H6831 are structurally similar and both target the C-terminal of OspB. ##H6831 consists of a heavy and a light chain and each chain is composed of a variable and a constant domain.## The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)##

===Lys-253===
<scene name='Studio:G1SecL01/Lys253/1'>and here is Lys253</scene> doing its thing.

<scene name='Studio:G1SecL01/Lys_253/1'>Lys 253 updated</scene>

<scene name='Studio:G1SecL01/Lys_modified/1'>crazy lys which one is better</scene>

<scene name='Studio:G1SecL01/Loop2/1'>Loop 2</scene>

<Structure load='1FJ1' size='300' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

==Homologous Structures in OspA===

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-24T22:06:32Z

Safa Abdelhakim:

==Introduction==
The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease|Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi| Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete| spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/| Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to complement-dependent lysis. Lysis in the absence of complement is necessary to clear ''Borrelia burgdorferi''. Certain Fragment Antigen Binding (fab) fragments of antibody are bactericidal even in the absence of a complement. The binding of specific fabs of IgG and IgM monoclonal antibodies to OspA and OspB of the ''Borrelia'' leads to a complement-independent lysis of the bacteria. <ref>PMID:15864264</ref>

<Structure load='1RJL' size='300' frame='true' align='right' caption='OspB_H6831' scene='Studio:G1SecL01/Ospb_h6831_complex/2' />

==Interaction With OspB==
===OspB + H6831===

<scene name='Studio:G1SecL01/Ospb_h6831_complex/2'>Restore original scene</scene>

<scene name='Studio:G1SecL01/Ospb/2'>OspB</scene>

IgG antibody fabs CB2 and H6831 are structurally similar and both target the C-terminal of OspB. ##H6831 consists of a heavy and a light chain and each chain is composed of a variable and a constant domain.## The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)##

===Lys-253===
<scene name='Studio:G1SecL01/Lys253/1'>and here is Lys253</scene> doing its thing.

<scene name='Studio:G1SecL01/Lys_253/1'>Lys 253 updated</scene>

<scene name='Studio:G1SecL01/Loop2/1'>Loop 2</scene>

<Structure load='1FJ1' size='300' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

==Homologous Structures in OspA===

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-24T21:42:26Z

Safa Abdelhakim:

==Introduction==
The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease|Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi| Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete| spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/| Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to complement-dependent lysis. Lysis in the absence of complement is necessary to clear ''Borrelia burgdorferi''. Certain Fragment Antigen Binding (fab) fragments of antibody are bactericidal even in the absence of a complement. The binding of specific fabs of IgG and IgM monoclonal antibodies to OspA and OspB of the ''Borrelia'' leads to a complement-independent lysis of the bacteria. <ref>PMID:15864264</ref>

<Structure load='1RJL' size='300' frame='true' align='right' caption='OspB_H6831' scene='Studio:G1SecL01/Ospb_h6831_complex/2' />

==Interaction With OspB==
===OspB + H6831===

<scene name='Studio:G1SecL01/Ospb_h6831_complex/2'>Restore original scene</scene>

<scene name='Studio:G1SecL01/Ospb/2'>OspB</scene>

IgG antibody fabs CB2 and H6831 are structurally similar and both target the C-terminal of OspB. ##H6831 consists of a heavy and a light chain and each chain is composed of a variable and a constant domain.## The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)##

===Lys-253===
<scene name='Studio:G1SecL01/Lys253/1'>and here is Lys253</scene> doing its thing.

<scene name='Studio:G1SecL01/Loop2/1'>Loop 2</scene>

<Structure load='1FJ1' size='300' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

==Homologous Structures in OspA===

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-24T21:41:30Z

Safa Abdelhakim:

==Introduction==
The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease|Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi| Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete| spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/| Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to complement-dependent lysis. Lysis in the absence of complement is necessary to clear ''Borrelia burgdorferi''. Certain Fragment Antigen Binding (fab) fragments of antibody are bactericidal even in the absence of a complement. The binding of specific fabs of IgG and IgM monoclonal antibodies to OspA and OspB of the ''Borrelia'' leads to a complement-independent lysis of the bacteria. <ref>PMID:15864264</ref>

<Structure load='1RJL' size='300' frame='true' align='right' caption='OspB_H6831' scene='Studio:G1SecL01/Ospb_h6831_complex/2' />

==Interaction With OspB==
===OspB + H6831===

<scene name='Studio:G1SecL01/Ospb_h6831_complex/2'>Restore original scene</scene>

<scene name='Studio:G1SecL01/Ospb/2'>TextToBeDisplayed</scene>

<scene name='Studio:G1SecL01/Ospb/1'>OspB</scene>

IgG antibody fabs CB2 and H6831 are structurally similar and both target the C-terminal of OspB. ##H6831 consists of a heavy and a light chain and each chain is composed of a variable and a constant domain.## The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)##

===Lys-253===
<scene name='Studio:G1SecL01/Lys253/1'>and here is Lys253</scene> doing its thing.

<scene name='Studio:G1SecL01/Loop2/1'>Loop 2</scene>

<Structure load='1FJ1' size='300' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

==Homologous Structures in OspA===

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-24T21:36:13Z

Safa Abdelhakim:

==Introduction==
The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease|Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi| Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete| spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/| Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to complement-dependent lysis. Lysis in the absence of complement is necessary to clear ''Borrelia burgdorferi''. Certain Fragment Antigen Binding (fab) fragments of antibody are bactericidal even in the absence of a complement. The binding of specific fabs of IgG and IgM monoclonal antibodies to OspA and OspB of the ''Borrelia'' leads to a complement-independent lysis of the bacteria. <ref>PMID:15864264</ref>

<Structure load='1RJL' size='300' frame='true' align='right' caption='OspB_H6831' scene='Studio:G1SecL01/Ospb_h6831_complex/2' />

==Interaction With OspB==
===OspB + H6831===

<scene name='Studio:G1SecL01/Ospb_h6831_complex/2'>Restore original scene</scene>

<scene name='Studio:G1SecL01/Ospb/1'>OspB</scene>

IgG antibody fabs CB2 and H6831 are structurally similar and both target the C-terminal of OspB. ##H6831 consists of a heavy and a light chain and each chain is composed of a variable and a constant domain.## The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)##

===Lys-253===
<scene name='Studio:G1SecL01/Lys253/1'>and here is Lys253</scene> doing its thing.

<scene name='Studio:G1SecL01/Loop2/1'>Loop 2</scene>

<Structure load='1FJ1' size='300' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

==Homologous Structures in OspA===

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-24T21:08:12Z

Safa Abdelhakim:

==Introduction==
The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease|Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi| Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete| spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/| Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to complement-dependent lysis. Lysis in the absence of complement is necessary to clear ''Borrelia burgdorferi''. Certain Fragment Antigen Binding (fab) fragments of antibody are bactericidal even in the absence of a complement. The binding of specific fabs of IgG and IgM monoclonal antibodies to OspA and OspB of the ''Borrelia'' leads to a complement-independent lysis of the bacteria. <ref>PMID:15864264</ref>

<Structure load='1RJL' size='300' frame='true' align='right' caption='OspB_H6831' scene='Studio:G1SecL01/Ospb_h6831_complex/2' />

==Interaction With OspB==
===OspB + H6831===

<scene name='Studio:G1SecL01/Ospb_h6831_complex/2'>Restore original scene</scene>

<scene name='Studio:G1SecL01/Ospb_only/1'>show OspB</scene>

IgG antibody fabs CB2 and H6831 are structurally similar and both target the C-terminal of OspB. ##H6831 consists of a heavy and a light chain and each chain is composed of a variable and a constant domain.## The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)##

===Lys-253===
<scene name='Studio:G1SecL01/Lys253/1'>and here is Lys253</scene> doing its thing.

<scene name='Studio:G1SecL01/Loop2/1'>Loop 2</scene>

<Structure load='1FJ1' size='300' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

==Homologous Structures in OspA===

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-24T20:55:46Z

Safa Abdelhakim:

==Introduction==
The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease|Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi| Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete| spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/| Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to complement-dependent lysis. Lysis in the absence of complement is necessary to clear ''Borrelia burgdorferi''. Certain Fragment Antigen Binding (fab) fragments of antibody are bactericidal even in the absence of a complement. The binding of specific fabs of IgG and IgM monoclonal antibodies to OspA and OspB of the ''Borrelia'' leads to a complement-independent lysis of the bacteria. <ref>PMID:15864264</ref>

<Structure load='1RJL' size='300' frame='true' align='right' caption='hey buddy' scene='Studio:G1SecL01/Ospb_h6831_complex/2' />

==Interaction With OspB==
===OspB + H6831===

<scene name='Studio:G1SecL01/Ospb_h6831_complex/2'>Restore original scene</scene>

<scene name='Studio:G1SecL01/Ospb_only/1'>show OspB</scene>

IgG antibody fabs CB2 and H6831 are structurally similar and both target the C-terminal of OspB. ##H6831 consists of a heavy and a light chain and each chain is composed of a variable and a constant domain.## The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)##

===Lys-253===
<scene name='Studio:G1SecL01/Lys253/1'>and here is Lys253</scene> doing its thing.

<scene name='Studio:G1SecL01/Loop2/1'>Loop 2</scene>

<Structure load='1FJ1' size='300' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

==Homologous Structures in OspA===

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-24T20:54:21Z

Safa Abdelhakim:

==Introduction==
The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease|Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi| Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete| spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/| Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to complement-dependent lysis. Lysis in the absence of complement is necessary to clear ''Borrelia burgdorferi''. Certain Fragment Antigen Binding (fab) fragments of antibody are bactericidal even in the absence of a complement. The binding of specific fabs of IgG and IgM monoclonal antibodies to OspA and OspB of the ''Borrelia'' leads to a complement-independent lysis of the bacteria. <ref>PMID:15864264</ref>

<Structure load='1RJL' size='300' frame='true' align='right' caption='hey buddy' scene='Studio:G1SecL01/Ospb_h6831_complex/1' />

==Interaction With OspB==
===OspB + H6831===

<scene name='Studio:G1SecL01/Ospb_h6831_complex/2'>Restore original scene</scene>

<scene name='Studio:G1SecL01/Ospb_only/2'>show OspB</scene>

IgG antibody fabs CB2 and H6831 are structurally similar and both target the C-terminal of OspB. ##H6831 consists of a heavy and a light chain and each chain is composed of a variable and a constant domain.## The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)##

===Lys-253===
<scene name='Studio:G1SecL01/Lys253/1'>and here is Lys253</scene> doing its thing.

<scene name='Studio:G1SecL01/Loop2/1'>Loop 2</scene>

<Structure load='1FJ1' size='300' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

==Homologous Structures in OspA===

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-24T20:43:15Z

Safa Abdelhakim:

==Introduction==
The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease|Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi| Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete| spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/| Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to complement-dependent lysis. Lysis in the absence of complement is necessary to clear ''Borrelia burgdorferi''. Certain Fragment Antigen Binding (fab) fragments of antibody are bactericidal even in the absence of a complement. The binding of specific fabs of IgG and IgM monoclonal antibodies to OspA and OspB of the ''Borrelia'' leads to a complement-independent lysis of the bacteria. <ref>PMID:15864264</ref>

<Structure load='1RJL' size='300' frame='true' align='right' caption='hey buddy' scene='Studio:G1SecL01/Ospb_h6831_complex/1' />

==Interaction With OspB==
===OspB + H6831===

<scene name='Studio:G1SecL01/Ospb_h6831_complex/1'>Restore original scene</scene>

<scene name='Studio:G1SecL01/Ospb_only/1'>show OspB</scene>

IgG antibody fabs CB2 and H6831 are structurally similar and both target the C-terminal of OspB. ##H6831 consists of a heavy and a light chain and each chain is composed of a variable and a constant domain.## The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)##

===Lys-253===
<scene name='Studio:G1SecL01/Lys253/1'>and here is Lys253</scene> doing its thing.

<scene name='Studio:G1SecL01/Loop2/1'>Loop 2</scene>

<Structure load='1FJ1' size='300' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

==Homologous Structures in OspA===

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-24T20:26:02Z

Safa Abdelhakim:

==Introduction==
The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease|Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi| Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete| spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/| Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to complement-dependent lysis. Lysis in the absence of complement is necessary to clear ''Borrelia burgdorferi''. Certain Fragment Antigen Binding (fab) fragments of antibody are bactericidal even in the absence of a complement. The binding of specific fabs of IgG and IgM monoclonal antibodies to OspA and OspB of the ''Borrelia'' leads to a complement-independent lysis of the bacteria. <ref>PMID:15864264</ref>

<Structure load='1RJL' size='300' frame='true' align='right' caption='hey buddy' scene='Insert optional scene name here' />

==Interaction With OspB==
===OspB + H6831===

<scene name='Studio:G1SecL01/Ospb_only/1'>show OspB</scene>

IgG antibody fabs CB2 and H6831 are structurally similar and both target the C-terminal of OspB. ##H6831 consists of a heavy and a light chain and each chain is composed of a variable and a constant domain.## The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)##

===Lys-253===
<scene name='Studio:G1SecL01/Lys253/1'>and here is Lys253</scene> doing its thing.

<scene name='Studio:G1SecL01/Loop2/1'>Loop 2</scene>

<Structure load='1FJ1' size='300' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

==Homologous Structures in OspA===

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-24T20:03:07Z

Safa Abdelhakim:

==Introduction==
The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease|Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi| Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete| spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/| Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to complement-dependent lysis. Lysis in the absence of complement is necessary to clear ''Borrelia burgdorferi''. Certain Fragment Antigen Binding (fab) fragments of antibody are bactericidal even in the absence of a complement. The binding of specific fabs of IgG and IgM monoclonal antibodies to OspA and OspB of the ''Borrelia'' leads to a complement-independent lysis of the bacteria. <ref>PMID:15864264</ref>

<Structure load='1P4B' size='300' frame='true' align='right' caption='OspB C terminal' scene='Insert optional scene name here' />

==Interaction With OspB==
===OspB + H6831===
<Structure load='1RJL' size='300' frame='true' align='right' caption='hey buddy' scene='Insert optional scene name here' />

IgG antibody fabs CB2 and H6831 are structurally similar and both target the C-terminal of OspB. ##H6831 consists of a heavy and a light chain and each chain is composed of a variable and a constant domain.## The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)##

===Lys-253===
<scene name='Studio:G1SecL01/Lys253/1'>and here is Lys253</scene> doing its thing.

<Structure load='1FJ1' size='300' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

<scene name='Studio:G1SecL01/Loop_2/4'>Loop 2</scene>

==Homologous Structures in OspA===

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-24T12:21:05Z

Safa Abdelhakim:

==Introduction==
The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease|Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi| Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete| spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/| Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to complement-dependent lysis. Lysis in the absence of complement is necessary to clear ''Borrelia burgdorferi''. Certain Fragment Antigen Binding (fab) fragments of antibody are bactericidal even in the absence of a complement. The binding of specific fabs of IgG and IgM monoclonal antibodies to OspA and OspB of the ''Borrelia'' leads to a complement-independent lysis of the bacteria. <ref>PMID:15864264</ref>

<Structure load='1P4B' size='300' frame='true' align='right' caption='OspB C terminal' scene='Insert optional scene name here' />

==Interaction With OspB==
===OspB + H6831===
<Structure load='1RJL' size='500' frame='true' align='right' caption='hey buddy' scene='Insert optional scene name here' />

IgG antibody fabs CB2 and H6831 are structurally similar and both target the C-terminal of OspB. ##H6831 consists of a heavy and a light chain and each chain is composed of a variable and a constant domain.## The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)##

===Lys-253===
<scene name='Studio:G1SecL01/Lys253/1'>and here is Lys253</scene> doing its thing.

<Structure load='1FJ1' size='300' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

<scene name='Studio:G1SecL01/Loop_2/4'>Loop 2</scene>

==Homologous Structures in OspA===

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-24T03:34:59Z

Safa Abdelhakim:

==Introduction==
The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease|Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi| Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete| spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/| Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to complement-dependent lysis. Lysis in the absence of complement is necessary to clear ''Borrelia burgdorferi''. Certain Fragment Antigen Binding (fab) fragments of antibody are bactericidal even in the absence of a complement. The binding of specific fabs of IgG and IgM monoclonal antibodies to OspA and OspB of the ''Borrelia'' leads to a complement-independent lysis of the bacteria. <ref>PMID:15864264</ref>

==Interaction With OspB==
===1FJ1- OspB + H6831===
<Structure load='1RJL' size='500' frame='true' align='right' caption='hey buddy' scene='Insert optional scene name here' />

IgG antibody fabs CB2 and H6831 are structurally similar and both target the C-terminal of OspB. ##H6831 consists of a heavy and a light chain and each chain is composed of a variable and a constant domain.## The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)##

===Lys-253===
<scene name='Studio:G1SecL01/Lys253/1'>and here is Lys253</scene> doing its thing.

<Structure load='1FJ1' size='300' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

<scene name='Studio:G1SecL01/Loop_2/4'>Loop 2</scene>

==Homologous Structures in OspA===

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-24T02:52:45Z

Safa Abdelhakim: /* Lys-253 */

==Introduction==
The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease|Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi| Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete| spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/| Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to complement-dependent lysis. Lysis in the absence of complement is necessary to clear ''Borrelia burgdorferi''. Certain Fragment Antigen Binding (fab) fragments of antibody are bactericidal even in the absence of a complement. The binding of specific fabs of IgG and IgM monoclonal antibodies to OspA and OspB of the ''Borrelia'' leads to a complement-independent lysis of the bacteria. <ref>PMID:15864264</ref>

==Interaction With OspB==
===1FJ1- OspB + H6831===
<Structure load='1RJL' size='500' frame='true' align='right' caption='hey buddy' scene='Insert optional scene name here' />

IgG antibody fabs CB2 and H6831 are structurally similar and both target the C-terminal of OspB. ##H6831 consists of a heavy and a light chain and each chain is composed of a variable and a constant domain.## The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)##

===Lys-253===
<scene name='Studio:G1SecL01/Lys253/1'>and here is Lys253</scene> doing its thing.

<Structure load='1FJ1' size='300' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

==Homologous Structures in OspA===

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-24T02:51:49Z

Safa Abdelhakim:

==Introduction==
The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease|Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi| Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete| spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/| Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to complement-dependent lysis. Lysis in the absence of complement is necessary to clear ''Borrelia burgdorferi''. Certain Fragment Antigen Binding (fab) fragments of antibody are bactericidal even in the absence of a complement. The binding of specific fabs of IgG and IgM monoclonal antibodies to OspA and OspB of the ''Borrelia'' leads to a complement-independent lysis of the bacteria. <ref>PMID:15864264</ref>

==Interaction With OspB==
===1FJ1- OspB + H6831===
<Structure load='1RJL' size='500' frame='true' align='right' caption='hey buddy' scene='Insert optional scene name here' />

IgG antibody fabs CB2 and H6831 are structurally similar and both target the C-terminal of OspB. ##H6831 consists of a heavy and a light chain and each chain is composed of a variable and a constant domain.## The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)##

===Lys-253===
<scene name='Studio:G1SecL01/Lys253/1'>and here is Lys253</scene> doing its thing.

<Structure load='1FJ1' size='500' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

==Homologous Structures in OspA===

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-23T21:34:33Z

Safa Abdelhakim:

==Introduction==
The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease|Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi| Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete| spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/| Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to complement-dependent lysis. Lysis in the absence of complement is necessary to clear ''Borrelia burgdorferi''. Certain Fragment Antigen Binding (fab) fragments of antibody are bactericidal even in the absence of a complement. The binding of specific fabs of IgG and IgM monoclonal antibodies to OspA and OspB of the ''Borrelia'' leads to a complement-independent lysis of the bacteria. <ref>PMID:15864264</ref>

==Interaction With OspB==
===1FJ1- OspB + H6831===
<Structure load='1RJL' size='500' frame='true' align='right' caption='hey buddy' scene='Insert optional scene name here' />

IgG antibody fabs CB2 and H6831 are structurally similar and both target the C-terminal of OspB. ##H6831 consists of a heavy and a light chain and each chain is composed of a variable and a constant domain.## The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)##

===Lys-253===
<scene name='Studio:G1SecL01/Lys253/1'>and here is Lys253</scene> doing its thing.

<Structure load='1FJ1' size='500' frame='true' align='right' caption='OspA-LA2 Complex' scene='Insert optional scene name here' />

<Structure load='1RJL' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />

==Homologous Structures in OspA===

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-23T21:33:37Z

Safa Abdelhakim:

==Introduction==
The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease|Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi| Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete| spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/| Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to complement-dependent lysis. Lysis in the absence of complement is necessary to clear ''Borrelia burgdorferi''. Certain Fragment Antigen Binding (fab) fragments of antibody are bactericidal even in the absence of a complement. The binding of specific fabs of IgG and IgM monoclonal antibodies to OspA and OspB of the ''Borrelia'' leads to a complement-independent lysis of the bacteria. <ref>PMID:15864264</ref>

==Interaction With OspB==
===1FJ1- OspB + H6831===
<Structure load='1RJL' size='500' frame='true' align='right' caption='hey buddy' scene='Insert optional scene name here' />

IgG antibody fabs CB2 and H6831 are structurally similar and both target the C-terminal of OspB. ##H6831 consists of a heavy and a light chain and each chain is composed of a variable and a constant domain.## The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)##

===Lys-253===
<scene name='Studio:G1SecL01/Lys253/1'>and here is Lys253</scene> doing its thing.

<Structure load='1FJ1' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />

<Structure load='1RJL' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />

==Homologous Structures in OspA===

User:Marvin O'Neal/Antibody OspA and OspB

2012-04-23T21:17:01Z

Safa Abdelhakim:

==Introduction==
The causative agent of [http://en.wikipedia.org/wiki/Lyme_disease|Lyme disease] is ''[http://en.wikipedia.org/wiki/Borrelia_burgdorferi| Borellia burgdorferi]'', a [http://en.wikipedia.org/wiki/Spirochaete| spirochaete] found in the gut of hard bodied ticks of genus ''[http://en.wikipedia.org/wiki/| Ixodes]''. A factor contributing to the severity of Lyme disease is its resistance to complement-dependent lysis. Lysis in the absence of complement is necessary to clear ''Borrelia burgdorferi''. Certain Fragment Antigen Binding (fab) fragments of antibody are bactericidal even in the absence of a complement. The binding of specific fabs of IgG and IgM monoclonal antibodies to OspA and OspB of the ''Borrelia'' leads to a complement-independent lysis of the bacteria. <ref>PMID:15864264</ref>

==Interaction With OspB==
===1FJ1- OspB + H6831===
<Structure load='1RJL' size='500' frame='true' align='right' caption='hey buddy' scene='Insert optional scene name here' />

IgG antibody fabs CB2 and H6831 are structurally similar and both target the C-terminal of OspB. ##H6831 consists of a heavy and a light chain and each chain is composed of a variable and a constant domain.## The paratope is located at the N terminal of the variable region of both the heavy and the light chains (Putnam 1979). Fab binding destabilizes the outer membrane (OM) of ''B. burdorferi'' with subsequent formation of spheroplasts. It has been observed that the bactericidal action upon binding requires the presence of bivalent cations (Mg2+ and Ca2+). When a similar fab, CB2, is bound to OspB, channels open in the OM allowing rapid infusion of electrolytes,increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades <ref>PMID:9125579</ref>

##When bound to a similar fab CB2, OspB-CB2 complexes could create physical openings in the OM allowing for rapid infusion of electrolytes, increasing the osmolarity of the periplasm and triggering bivalent cation dependent cascades (Escudero; Halluska et al. 1997)##

===Lys-253===
<scene name='Studio:G1SecL01/Lys253/1'>and here is Lys253</scene> doing its thing.

<Structure load='1RJL' size='500' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />

==Homologous Structures in OspA===