Sandbox Reserved 200

2011-03-31T17:05:43Z

Lexi Gehring:

{{Template:Johnson_CH462_Spring2011}}


=Introduction=
[[Image:2D_RNase_A.png|200px|left|thumb|RNase A minor dimer,[[1A2W]]]]
Bovine pancreatic ribonuclease A [http://en.wikipedia.org/wiki/Ribonuclease_A (RNase A)] is an enzyme that catalyzes the hydrolysis of RNA through [http://www.proteopedia.org/wiki/index.php/Sandbox_Reserved_193 acid-base catalysis]. RNase A has the capability to structurally form dimers, trimers, and other oligomers based on the structure of the [http://www.proteopedia.org/wiki/index.php/Sandbox_Reserved_192 RNase A monomer]. Unlike the monomers, these oligomers are capable of catalyzing the hydrolysis of double stranded RNA (dsRNA).<ref name="tumor">PMID:12697760</ref> The oligomers are formed by 3D domain swapping, which can occur once or twice per monomeric unit <ref name="liul">PMID:11224563</ref >. The 3D domain swapping has no impact on the formation of active sites which is the same in the monomers and all oligomers.<ref name="liul"/> The oligomers of RNase A also show medical relevance when looking at antitumor drugs as well as the possible cause of Alzheimer's.

=Dimers=
<Structure load='1A2W' size='400' frame='true' align='right' caption='Ribonuclease A Dimer' scene='Sandbox_Reserved_200/Minor_dimer/2' />
Ribonuclease A has both a major and <scene name='Sandbox_Reserved_200/Minor_dimer/2'>Minor dimer</scene> which are very similar to one another. Though they are similar, they are formed by different types of 3D domain swapping. 3D domain swapping occurs when identical domains are interchanged. The <scene name='Sandbox_Reserved_200/Major_dimer/11'>Major dimer</scene> is formed by 3D domain swapping the β-strand of the C-terminus.<ref name="liu98"/> The minor dimer, on the other hand, is formed by 3D domain swapping its α-helix of the N-terminus <ref name="liu98"/>. Domain swapping is extremely specific and can only occur at the <scene name='Sandbox_Reserved_200/Major_dimer/10'>C-terminus</scene> or the <scene name='Sandbox_Reserved_200/Major_dimer/9'>N-terminus</scene>.

The two domains of the dimer are linked via the hinge loop.<ref name="liul"/>. In the major dimer, the hinge loop is composed of residues 112-115. In the minor dimer, the hinge loop is composed of residues 16-22.<ref name="liul"/> The most important component of the hinge loops is Ala19. <scene name='Sandbox_Reserved_200/Minor_dimer_hinge/1'>Ala19</scene> is the reason that the hinge loops are so flexible . This flexibility allows the dimers to adopt different orientations, for example the major and minor structures.<ref name="liu98"/>

=Trimers=
<Structure load='1JS0' size='400' frame='true' align='left' caption='Minor Trimer of RNase A' scene='Sandbox_Reserved_200/Minor_trimer/1' />

=Medical Relevance=

[http://en.wikipedia.org/wiki/Alzheimer%27s_disease Alzheimer’s disease] is a terminal disease that slowly degenerates the brain. One of the possible causes of Alzheimer’s is [http://en.wikipedia.org/wiki/Amyloid amyloid] deposits throughout the brain. Though RNasa A oligomers are not the amyloid deposits that cause Alzheimer’s the folding of these oligomers gives clues towards the formation of amyloid deposits responsible for Alzheimer’s.

The 3D domain swapping has many similarities with the formation of amyloid fibers. Both are highly specific reactions coming from only one type of monomer and these reactions can form linear aggregates. <ref name="liu01"/> These aggregates of proteins are formed by hydrogen bonding at the hinge loops which form an antiparalell β-pleated sheet. <ref name="liu01"/> This most commonly happens with the major dimer. Liu suggests that all proteins are capable of forming aggregates by domain swapping as long as they are in high concentration and partially destabilized. <ref name="liu01"/> As 3D domain swapping becomes more understood, it will offer insight to the amyloid formation in Alzheimer’s patients.

The RNase A 3D domain swapped oligomers show significant biological activity including allostery, antitumor, and immunorepression activity. In antitumor activity, the oligomers degrade dsRNA, but they are also capable of degrading DNA and RNA hybrids which can be found during the translation of genes.<ref name="tumor"/> This same activity has not observed in the monomer and the non-3D domain swapped oligomers .<ref name="liu98">PMID:9502384</ref > This could be due to the fact that the monomer has a cystolic RNase A inhibitor that is unable to inhibit the active sites of the oligomers. <ref name="liu01">PMID:11790847</ref >

All oligomers of RNase A have antitumor activity, but the higher ordered oligomers show greater activity. <ref name="tumor"/> Though the higher ordered oligomers are more active, they are also much more unstable when ''in vivo''. The pathway of the oligomer once it is inside the cell is unknown, but they do seem to be unregulated. <ref name="tumor"/> In cancer cells because the movement of proteins into the nucleus is unregulated, oligomers can sometimes enter into the nucleus. Once the oligomer is in the nucleus, it is able to degrade RNA and DNA hybrids.<ref name="tumor"/> This will eventually prevent the cell from dividing and decrease the tumor size. Before using oligomers as an antitumor drug, the pathway of the oligomers into and in the cell needs to be monitored so that the oligomers do not degrade dsRNA in healthy cells.

=Literature Cited=

<references />

=External Links=
[http://en.wikipedia.org/wiki/Ribonuclease_A Wikipedia Ribonuclease A]

[http://www.proteopedia.org/wiki/index.php/Sandbox_Reserved_192 Structure of RNase A monomer]

[http://www.proteopedia.org/wiki/index.php/Sandbox_Reserved_193 Acid-base catalysis of RNase A]

[http://en.wikipedia.org/wiki/Alzheimer%27s_disease Wikipedia Alzheimer’s disease]

Sandbox Reserved 200

2011-03-31T17:03:10Z

Lexi Gehring:

{{Template:Johnson_CH462_Spring2011}}


=Introduction=
[[Image:2D_RNase_A.png|200px|left|thumb|RNase A minor dimer,[[1A2W]]]]
Bovine pancreatic ribonuclease A [http://en.wikipedia.org/wiki/Ribonuclease_A (RNase A)] is an enzyme that catalyzes the hydrolysis of RNA through [http://www.proteopedia.org/wiki/index.php/Sandbox_Reserved_193 acid-base catalysis]. RNase A has the capability to structurally form dimers, trimers, and other oligomers based on the structure of the [http://www.proteopedia.org/wiki/index.php/Sandbox_Reserved_192 RNase A monomer]. Unlike the monomers, these oligomers are capable of catalyzing the hydrolysis of double stranded RNA (dsRNA).<ref name="tumor">PMID:12697760</ref> The oligomers are formed by 3D domain swapping, which can occur once or twice per monomeric unit <ref name="liul">PMID:11224563</ref >. The 3D domain swapping has no impact on the formation of active sites. These same active sites, which are composed of His 12, Lys 41, and His 119, can be found in the monomer, dimer, and trimer <ref name="liul"/>. The oligomers of RNase A also show medical relevance when looking at antitumor drugs as well as the possible cause of Alzheimer's.

=Dimers=
<Structure load='1A2W' size='400' frame='true' align='right' caption='Ribonuclease A Dimer' scene='Sandbox_Reserved_200/Minor_dimer/2' />
Ribonuclease A has both a major and <scene name='Sandbox_Reserved_200/Minor_dimer/2'>Minor dimer</scene> which are very similar to one another. Though they are similar, they are formed by different types of 3D domain swapping. 3D domain swapping occurs when identical domains are interchanged. The <scene name='Sandbox_Reserved_200/Major_dimer/11'>Major dimer</scene> is formed by 3D domain swapping the β-strand of the C-terminus.<ref name="liu98"/> The minor dimer, on the other hand, is formed by 3D domain swapping its α-helix of the N-terminus <ref name="liu98"/>. Domain swapping is extremely specific and can only occur at the <scene name='Sandbox_Reserved_200/Major_dimer/10'>C-terminus</scene> or the <scene name='Sandbox_Reserved_200/Major_dimer/9'>N-terminus</scene>.

The two domains of the dimer are linked via the hinge loop.<ref name="liul"/>. In the major dimer, the hinge loop is composed of residues 112-115. In the minor dimer, the hinge loop is composed of residues 16-22.<ref name="liul"/> The most important component of the hinge loops is Ala19. <scene name='Sandbox_Reserved_200/Minor_dimer_hinge/1'>Ala19</scene> is the reason that the hinge loops are so flexible . This flexibility allows the dimers to adopt different orientations, for example the major and minor structures.<ref name="liu98"/>

=Trimers=
<Structure load='1JS0' size='400' frame='true' align='left' caption='Minor Trimer of RNase A' scene='Sandbox_Reserved_200/Minor_trimer/1' />

=Medical Relevance=

[http://en.wikipedia.org/wiki/Alzheimer%27s_disease Alzheimer’s disease] is a terminal disease that slowly degenerates the brain. One of the possible causes of Alzheimer’s is [http://en.wikipedia.org/wiki/Amyloid amyloid] deposits throughout the brain. Though RNasa A oligomers are not the amyloid deposits that cause Alzheimer’s the folding of these oligomers gives clues towards the formation of amyloid deposits responsible for Alzheimer’s.

The 3D domain swapping has many similarities with the formation of amyloid fibers. Both are highly specific reactions coming from only one type of monomer and these reactions can form linear aggregates. <ref name="liu01"/> These aggregates of proteins are formed by hydrogen bonding at the hinge loops which form an antiparalell β-pleated sheet. <ref name="liu01"/> This most commonly happens with the major dimer. Liu suggests that all proteins are capable of forming aggregates by domain swapping as long as they are in high concentration and partially destabilized. <ref name="liu01"/> As 3D domain swapping becomes more understood, it will offer insight to the amyloid formation in Alzheimer’s patients.

The RNase A 3D domain swapped oligomers show significant biological activity including allostery, antitumor, and immunorepression activity. In antitumor activity, the oligomers degrade dsRNA, but they are also capable of degrading DNA and RNA hybrids which can be found during the translation of genes.<ref name="tumor"/> This same activity has not observed in the monomer and the non-3D domain swapped oligomers .<ref name="liu98">PMID:9502384</ref > This could be due to the fact that the monomer has a cystolic RNase A inhibitor that is unable to inhibit the active sites of the oligomers. <ref name="liu01">PMID:11790847</ref >

All oligomers of RNase A have antitumor activity, but the higher ordered oligomers show greater activity. <ref name="tumor"/> Though the higher ordered oligomers are more active, they are also much more unstable when ''in vivo''. The pathway of the oligomer once it is inside the cell is unknown, but they do seem to be unregulated. <ref name="tumor"/> In cancer cells because the movement of proteins into the nucleus is unregulated, oligomers can sometimes enter into the nucleus. Once the oligomer is in the nucleus, it is able to degrade RNA and DNA hybrids.<ref name="tumor"/> This will eventually prevent the cell from dividing and decrease the tumor size. Before using oligomers as an antitumor drug, the pathway of the oligomers into and in the cell needs to be monitored so that the oligomers do not degrade dsRNA in healthy cells.

=Literature Cited=

<references />

=External Links=
[http://en.wikipedia.org/wiki/Ribonuclease_A Wikipedia Ribonuclease A]

[http://www.proteopedia.org/wiki/index.php/Sandbox_Reserved_192 Structure of RNase A monomer]

[http://www.proteopedia.org/wiki/index.php/Sandbox_Reserved_193 Acid-base catalysis of RNase A]

[http://en.wikipedia.org/wiki/Alzheimer%27s_disease Wikipedia Alzheimer’s disease]

Sandbox Reserved 200

2011-03-31T16:10:15Z

Lexi Gehring:

{{Template:Johnson_CH462_Spring2011}}


=Introduction=
[[Image:2D_RNase_A.png|200px|left|thumb|RNase A minor dimer,[[1A2W]]]]
Bovine pancreatic ribonuclease A [http://en.wikipedia.org/wiki/Ribonuclease_A (RNase A)] is an enzyme that catalyzes the hydrolysis of RNA through [http://www.proteopedia.org/wiki/index.php/Sandbox_Reserved_193 acid-base catalysis]. RNase A has the capability to structurally form dimers, trimers, and other oligomers based on the structure of the [http://www.proteopedia.org/wiki/index.php/Sandbox_Reserved_192 Structure of RNase A monomer]. Unlike the monomers, these oligomers are capable of catalyzing the hydrolysis of double stranded RNA (dsRNA).<ref name="tumor">PMID:12697760</ref> The oligomers are formed by 3D domain swapping, which can occur once or twice per monomeric unit <ref name="liul">PMID:11224563</ref >. The 3D domain swapping has no impact on the formation of active sites. These same active sites, which are composed of His 12, Lys 41, and His 119, can be found in the monomer, dimer, and trimer <ref name="liul"/>. The oligomers of RNase A also show medical relevance when looking at antitumor drugs as well as the possible cause of Alzheimer's.

=Dimers=
<Structure load='1A2W' size='400' frame='true' align='right' caption='Ribonuclease A Dimer' scene='Sandbox_Reserved_200/Minor_dimer/2' />
Ribonuclease A has both a major and <scene name='Sandbox_Reserved_200/Minor_dimer/2'>Minor dimer</scene> which are very similar to one another. Though they are similar, they are formed by different types of 3D domain swapping. 3D domain swapping occurs when identical domains are interchanged. The <scene name='Sandbox_Reserved_200/Major_dimer/11'>Major dimer</scene> is formed by 3D domain swapping the β-strand of the C-terminus.<ref name="liu98"/> The minor dimer, on the other hand, is formed by 3D domain swapping its α-helix of the N-terminus <ref name="liu98"/>. Domain swapping is extremely specific and can only occur at the <scene name='Sandbox_Reserved_200/Major_dimer/10'>C-terminus</scene> or the <scene name='Sandbox_Reserved_200/Major_dimer/9'>N-terminus</scene>.

The two domains of the dimer are linked via the hinge loop.<ref name="liul"/>. In the major dimer, the hinge loop is composed of residues 112-115. In the minor dimer, the hinge loop is composed of residues 16-22.<ref name="liul"/> The most important component of the hinge loops is Ala19. <scene name='Sandbox_Reserved_200/Minor_dimer_hinge/1'>Ala19</scene> is the reason that the hinge loops are so flexible . This flexibility allows the dimers to adopt different orientations, for example the major and minor structures.<ref name="liu98"/>

=Trimers=
<Structure load='1JS0' size='400' frame='true' align='left' caption='Minor Trimer of RNase A' scene='Sandbox_Reserved_200/Minor_trimer/1' />

=Medical Relevance=

[http://en.wikipedia.org/wiki/Alzheimer%27s_disease Alzheimer’s disease] is a terminal disease that slowly degenerates the brain. One of the possible causes of Alzheimer’s is [http://en.wikipedia.org/wiki/Amyloid amyloid] deposits throughout the brain. Though RNasa A oligomers are not the amyloid deposits that cause Alzheimer’s the folding of these oligomers gives clues towards the formation of amyloid deposits responsible for Alzheimer’s.

The 3D domain swapping has many similarities with the formation of amyloid fibers. Both are highly specific reactions coming from only one type of monomer and these reactions can form linear aggregates. <ref name="liu01"/> These aggregates of proteins are formed by hydrogen bonding at the hinge loops which form an antiparalell β-pleated sheet. <ref name="liu01"/> This most commonly happens with the major dimer. Liu suggests that all proteins are capable of forming aggregates by domain swapping as long as they are in high concentration and partially destabilized. <ref name="liu01"/> As 3D domain swapping becomes more understood, it will offer insight to the amyloid formation in Alzheimer’s patients.

The RNase A 3D domain swapped oligomers show significant biological activity including allostery, antitumor, and immunorepression activity. In antitumor activity, the oligomers degrade dsRNA, but they are also capable of degrading DNA and RNA hybrids which can be found during the translation of genes.<ref name="tumor"/> This same activity has not observed in the monomer and the non-3D domain swapped oligomers .<ref name="liu98">PMID:9502384</ref > This could be due to the fact that the monomer has a cystolic RNase A inhibitor that is unable to inhibit the active sites of the oligomers. <ref name="liu01">PMID:11790847</ref >

All oligomers of RNase A have antitumor activity, but the higher ordered oligomers show greater activity. <ref name="tumor"/> Though the higher ordered oligomers are more active, they are also much more unstable when ''in vivo''. The pathway of the oligomer once it is inside the cell is unknown, but they do seem to be unregulated. <ref name="tumor"/> In cancer cells because the movement of proteins into the nucleus is unregulated, oligomers can sometimes enter into the nucleus. Once the oligomer is in the nucleus, it is able to degrade RNA and DNA hybrids.<ref name="tumor"/> This will eventually prevent the cell from dividing and decrease the tumor size. Before using oligomers as an antitumor drug, the pathway of the oligomers into and in the cell needs to be monitored so that the oligomers do not degrade dsRNA in healthy cells.

=Literature Cited=

<references />

=External Links=
[http://en.wikipedia.org/wiki/Ribonuclease_A Wikipedia Ribonuclease A]

[http://www.proteopedia.org/wiki/index.php/Sandbox_Reserved_192 Structure of RNase A monomer]

[http://www.proteopedia.org/wiki/index.php/Sandbox_Reserved_193 Acid-base catalysis of RNase A]

[http://en.wikipedia.org/wiki/Alzheimer%27s_disease Wikipedia Alzheimer’s disease]