G15SecL05Tpc3: Difference between revisions

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==Lyme Disease==

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H6831 is a specific IgG class [http://www.en.wikipedia.org/wiki/Antigen antigen] binding fragment that has a series of significant residues that bind to the epitope on Osp-B and lyse it without the aid of a complement, resulting in a unique molecular interaction that causes a physical change in the shape of Osp-B upon binding. In order to better analyze the changes, crystallized structures of Osp-B and the Osp-B H6831 complex were taken and comparatively analyzed: X-ray diffraction showed that the structure of OspB-CT contains twelve anti parallel beta strands and a single alpha helix (Becker et al, 2005). Strands 1-4 form the Osp-B’s central sheet: this is a free standing sheet that is located at the N-terminus of the protein. The remaining strands 5-12 form two additional sheets that together with the alpha helix form a barrel-like domain. Analysis of the bound complex revealed that the central beta sheet is either destroyed or removed by proteolysis upon binding (Becker et al, 2005). Ultimately the structural changes to Osp-B appear to result only indirectly from the addition of Fab (Becker et al, 2005).

Almost the entirety of this binding process is centered around distinct residues that were discovered due to comparative analysis of Osp-A and Osp-B’s crystal structures. A charged triad is formed in both structures whose united physical form presents itself as a favorable binding site. In Osp-B, this triad consists of amino-acid residues Arg-162, Glu-184, and <scene name='G15SecL05Tpc3/Arg214/3'>Arg-214</scene> (with <scene name='G15SecL05Tpc3/Thr276/1'>Thr-276</scene> additionally aiding the binding process though not part of the triad). These residues form a prominent cleft with density void space in between each other. This space is well suited for an all trans-structures to bind into, and such a structure was located on the crystallized Osp-B-H6831 bound complex. This complex is a combination of Osp-B-CT residues 202-296 and the Fabs’ heavy and light chains. A notable feature of the OspB-CT-H6831 interaction is the prevalence of aromatic residues contributed by the Fab: these aromatic residues are the points at which Lys-253 on Osp-B guides itself to bind with <scene name='G15SecL05Tpc3/~~Realfab~~/1'>Glu-50</scene>. Specifically, Lys 253 wedges itself between residues Try-33 and Tyr-101 of the H6831 heavy chain to be able reach the Glu-50 so the ion-pair binding between the two residues can occur (Becker et al, 2005). This interaction, along with an amine hydrogen bond and ion pair with a glutamate from the Fab heavy chain, a second hydrogen bond with a main chain carbonyl from loop "1" of Osp-B-CT, and a water mediated hydrogen bond to a histidine from the Fab heavy chain constitute the three main series of interactions in the OspB-H6831 bound complex. Lys-253 is the absolute key component of the formation of this bound complex; if Lys-253 were to be substituted with another amino acid or be missing entirely via external influential mutation, the binding could not occur (Connolly et al, 2005).

Almost the entirety of this binding process is centered around distinct residues that were discovered due to comparative analysis of Osp-A and Osp-B’s crystal structures. A charged triad is formed in both structures whose united physical form presents itself as a favorable binding site. In Osp-B, this triad consists of amino-acid residues Arg-162, Glu-184, and <scene name='G15SecL05Tpc3/Arg214/3'>Arg-214</scene> (with <scene name='G15SecL05Tpc3/Thr276/1'>Thr-276</scene> additionally aiding the binding process though not part of the triad). These residues form a prominent cleft with density void space in between each other. This space is well suited for an all trans-structures to bind into, and such a structure was located on the crystallized Osp-B-H6831 bound complex. This complex is a combination of Osp-B-CT residues 202-296 and the Fabs’ heavy and light chains. A notable feature of the OspB-CT-H6831 interaction is the prevalence of aromatic residues contributed by the Fab: these aromatic residues are the points at which Lys-253 on Osp-B guides itself to bind with <scene name='G15SecL05Tpc3/Realfabtry/1'>Glu-50</scene>. Specifically, Lys 253 wedges itself between residues Try-33 and Tyr-101 of the H6831 heavy chain to be able reach the Glu-50 so the ion-pair binding between the two residues can occur (Becker et al, 2005). This interaction, along with an amine hydrogen bond and ion pair with a glutamate from the Fab heavy chain, a second hydrogen bond with a main chain carbonyl from loop "1" of Osp-B-CT, and a water mediated hydrogen bond to a histidine from the Fab heavy chain constitute the three main series of interactions in the OspB-H6831 bound complex. Lys-253 is the absolute key component of the formation of this bound complex; if Lys-253 were to be substituted with another amino acid or be missing entirely via external influential mutation, the binding could not occur (Connolly et al, 2005).

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G15SecL05Tpc3: Difference between revisions

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-<Structure load='1rjl' size='500' frame='true' align='right' caption='Osp-B Structure, Bound' scene='Insert optional scene name here' />
+<Structure load='1rjl' size='500' frame='true' align='right' caption='Structure of the complex between OspB-CT and bactericidal Fab-H6831' scene='Insert optional scene name here' />
 ==Lyme Disease==
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 H6831 is a specific IgG class [http://www.en.wikipedia.org/wiki/Antigen antigen] binding fragment that has a series of significant residues that bind to the epitope on Osp-B and lyse it without the aid of a complement, resulting in a unique molecular interaction that causes a physical change in the shape of Osp-B upon binding. In order to better analyze the changes, crystallized structures of Osp-B and the Osp-B H6831 complex were taken and comparatively analyzed: X-ray diffraction showed that the structure of OspB-CT contains twelve anti parallel beta strands and a single alpha helix (Becker et al, 2005). Strands 1-4 form the Osp-B’s central sheet: this is a free standing sheet that is located at the N-terminus of the protein. The remaining strands 5-12 form two additional sheets that together with the alpha helix form a barrel-like domain. Analysis of the bound complex revealed that the central beta sheet is either destroyed or removed by proteolysis upon binding (Becker et al, 2005). Ultimately the structural changes to Osp-B appear to result only indirectly from the addition of Fab (Becker et al, 2005).
-Almost the entirety of this binding process is centered around distinct residues that were discovered due to comparative analysis of Osp-A and Osp-B’s crystal structures. A charged triad is formed in both structures whose united physical form presents itself as a favorable binding site. In Osp-B, this triad consists of amino-acid residues Arg-162, Glu-184, and <scene name='G15SecL05Tpc3/Arg214/3'>Arg-214</scene> (with <scene name='G15SecL05Tpc3/Thr276/1'>Thr-276</scene> additionally aiding the binding process though not part of the triad). These residues form a prominent cleft with density void space in between each other. This space is well suited for an all trans-structures to bind into, and such a structure was located on the crystallized Osp-B-H6831 bound complex.  This complex is a combination of Osp-B-CT residues 202-296 and the Fabs’ heavy and light chains. A notable feature of the OspB-CT-H6831 interaction is the prevalence of aromatic residues contributed by the Fab: these aromatic residues are the points at which Lys-253 on Osp-B guides itself to bind with <scene name='G15SecL05Tpc3/Realfab/1'>Glu-50</scene>. Specifically, Lys 253 wedges itself between residues Try-33 and Tyr-101 of the H6831 heavy chain to be able reach the Glu-50 so the ion-pair binding between the two residues can occur (Becker et al, 2005). This interaction, along with an amine hydrogen bond and ion pair with a glutamate from the Fab heavy chain, a second hydrogen bond with a main chain carbonyl from loop "1" of Osp-B-CT, and a water mediated hydrogen bond to a histidine from the Fab heavy chain constitute the three main series of interactions in the OspB-H6831 bound complex. Lys-253 is the absolute key component of the formation of this bound complex; if Lys-253 were to be substituted with another amino acid or be missing entirely via external influential mutation, the binding could not occur (Connolly et al, 2005).
+Almost the entirety of this binding process is centered around distinct residues that were discovered due to comparative analysis of Osp-A and Osp-B’s crystal structures. A charged triad is formed in both structures whose united physical form presents itself as a favorable binding site. In Osp-B, this triad consists of amino-acid residues Arg-162, Glu-184, and <scene name='G15SecL05Tpc3/Arg214/3'>Arg-214</scene> (with <scene name='G15SecL05Tpc3/Thr276/1'>Thr-276</scene> additionally aiding the binding process though not part of the triad). These residues form a prominent cleft with density void space in between each other. This space is well suited for an all trans-structures to bind into, and such a structure was located on the crystallized Osp-B-H6831 bound complex.  This complex is a combination of Osp-B-CT residues 202-296 and the Fabs’ heavy and light chains. A notable feature of the OspB-CT-H6831 interaction is the prevalence of aromatic residues contributed by the Fab: these aromatic residues are the points at which Lys-253 on Osp-B guides itself to bind with <scene name='G15SecL05Tpc3/Realfabtry/1'>Glu-50</scene>. Specifically, Lys 253 wedges itself between residues Try-33 and Tyr-101 of the H6831 heavy chain to be able reach the Glu-50 so the ion-pair binding between the two residues can occur (Becker et al, 2005). This interaction, along with an amine hydrogen bond and ion pair with a glutamate from the Fab heavy chain, a second hydrogen bond with a main chain carbonyl from loop "1" of Osp-B-CT, and a water mediated hydrogen bond to a histidine from the Fab heavy chain constitute the three main series of interactions in the OspB-H6831 bound complex. Lys-253 is the absolute key component of the formation of this bound complex; if Lys-253 were to be substituted with another amino acid or be missing entirely via external influential mutation, the binding could not occur (Connolly et al, 2005).
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