Sandbox Reserved 200: Difference between revisions

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Similar to dimer, the structure of the monomer is conserved except for the <scene name='Sandbox_Reserved_200/Minor_trimer/2'>hinge loop</scene>. The <scene name='Sandbox_Reserved_200/Minor_trimer/3'>active sites</scene> of the trimers are made up of the same amino acid residues as the monomers and dimers. The trimer's active site is slightly different from that of the monomer and dimer because it has a sulfate ion trap.<ref name="liu01"/> A total of four sulfate ions bind to the minor trimer, three to the active sites, and one to the hinge loop. <scene name='Sandbox_Reserved_200/Minor_trimer/5'>Gly112</scene> residues from each subunit as well as other amino acid residues bind to the sulfate ion. An intricate network of hydrogen bonding holds the sulfate ion in the trap. <ref name="liu01"/> The monomers and dimers also have sulfate ions bond to their active site, but the ions seem to have a stronger presence within the trimer. The ions are bound to the active site are completely surrounded by water which is responsible for the <scene name='Sandbox_Reserved_200/Minor_trimer/7'>hydrogen bonding</scene> to the sulfate ion.

Similar to the dimer, the structure of the monomer is conserved except for the <scene name='Sandbox_Reserved_200/Minor_trimer/2'>hinge loop</scene>. The <scene name='Sandbox_Reserved_200/Minor_trimer/3'>active sites</scene> of the trimers are made up of the same amino acid residues as the monomers and dimers. The trimer's active site is slightly different from that of the monomer and dimer because it has a sulfate ion trap.<ref name="liu01"/> A total of four sulfate ions bind to the minor trimer, three to the active sites, and one to the hinge loop. <scene name='Sandbox_Reserved_200/Minor_trimer/5'>Gly112</scene> residues from each subunit as well as other amino acid residues bind to the sulfate ion. An intricate network of hydrogen bonding holds the sulfate ion in the trap. <ref name="liu01"/> The monomers and dimers also have sulfate ions bond to their active site, but the ions seem to have a stronger presence within the trimer. The ions are bound to the active site are completely surrounded by water, light blue spheres, which is responsible for the <scene name='Sandbox_Reserved_200/Minor_trimer/7'>hydrogen bonding</scene> to the sulfate ion.

==Enzymatic Activity==

The monomers, dimers, and trimers all have significant enzymatic activity. The higher the order of the oligomer, the ~~better~~ its enzymatic activity is.<ref name="liu01"/> The pentamers, though their structure is not known, have shown the ~~greatest~~ enzymatic activity. Though the ~~high~~ order oligomers are better enzymes, they are also degraded ~~to their subunits~~ faster~~. The~~ trimer will degrade to a dimer which will eventually degrade to a monomer.

The monomers, dimers, and trimers all have significant enzymatic activity. The higher the order of the oligomer, the higher its enzymatic activity.<ref name="liu01"/> The pentamers, though their structure is not known, have shown the highest enzymatic activity. Though the higher order oligomers are better enzymes, they are also degraded faster, where for instance the trimer will degrade to a dimer which will eventually degrade to a monomer.

The ~~major dimer is more active than the minor dimer, while the minor trimer~~ is ~~more active than the major trimer.<ref name="liu01"/> It has been shown that the smaller the distance~~ between ~~two~~ active sites~~, the greater the enzymatic activity on dsRNA~~. The higher ordered oligomers are typically more tightly packed which would decrease the distance between active sites, and make them more active.<ref name="liu01"/> Liu et. al. also predicts ~~taht teh~~ twisted orientation of the dimers and trimers allows for the destabilization of dsRNA. Because the monomer does not have a twisted structure, it is not able to destabilize dsRNA.<ref name="liu01"/>

The higher activity toward dsRNA is related to shorter distances between active sites. The higher ordered oligomers are typically more tightly packed which would decrease the distance between active sites, and make them more active.<ref name="liu01"/> For example, the major dimer is more active than the minor dimer, while the minor trimer is more active than the major trimer.<ref name="liu01"/> Liu et. al. also predicts that the twisted orientation of the dimers and trimers allows for the destabilization of dsRNA. Because the monomer does not have a twisted structure, it is not able to destabilize dsRNA.<ref name="liu01"/>

==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.

[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 RNase 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"/> Forty different proteins who form oligomers by 3D domain swapping have already been identified.<ref name="multimers">PMID:15104538</ref > As 3D domain swapping becomes more understood, it will offer insight to the amyloid formation in Alzheimer’s patients.

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 antiparallel 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"/> Forty different proteins who form oligomers by 3D domain swapping have already been identified.<ref name="multimers">PMID:15104538</ref > As 3D domain swapping becomes more understood, it will offer insight to the amyloid formation in Alzheimer’s patients.

Sandbox Reserved 200: Difference between revisions

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-Similar to dimer, the structure of the monomer is conserved except for the <scene name='Sandbox_Reserved_200/Minor_trimer/2'>hinge loop</scene>.  The <scene name='Sandbox_Reserved_200/Minor_trimer/3'>active sites</scene> of the trimers are made up of the same amino acid residues as the monomers and dimers.  The trimer's active site is slightly different from that of the monomer and dimer because it has a sulfate ion trap.<ref name="liu01"/>  A total of four sulfate ions bind to the minor trimer, three to the active sites, and one to the hinge loop.  <scene name='Sandbox_Reserved_200/Minor_trimer/5'>Gly112</scene> residues from each subunit as well as other amino acid residues bind to the sulfate ion.  An intricate network of hydrogen bonding holds the sulfate ion in the trap. <ref name="liu01"/>  The monomers and dimers also have sulfate ions bond to their active site, but the ions seem to have a stronger presence within the trimer.  The ions are bound to the active site are completely surrounded by water which is responsible for the <scene name='Sandbox_Reserved_200/Minor_trimer/7'>hydrogen bonding</scene> to the sulfate ion.
+Similar to the dimer, the structure of the monomer is conserved except for the <scene name='Sandbox_Reserved_200/Minor_trimer/2'>hinge loop</scene>.  The <scene name='Sandbox_Reserved_200/Minor_trimer/3'>active sites</scene> of the trimers are made up of the same amino acid residues as the monomers and dimers.  The trimer's active site is slightly different from that of the monomer and dimer because it has a sulfate ion trap.<ref name="liu01"/>  A total of four sulfate ions bind to the minor trimer, three to the active sites, and one to the hinge loop.  <scene name='Sandbox_Reserved_200/Minor_trimer/5'>Gly112</scene> residues from each subunit as well as other amino acid residues bind to the sulfate ion.  An intricate network of hydrogen bonding holds the sulfate ion in the trap. <ref name="liu01"/>  The monomers and dimers also have sulfate ions bond to their active site, but the ions seem to have a stronger presence within the trimer.  The ions are bound to the active site are completely surrounded by water, light blue spheres, which is responsible for the <scene name='Sandbox_Reserved_200/Minor_trimer/7'>hydrogen bonding</scene> to the sulfate ion.
 ==Enzymatic Activity==
-The monomers, dimers, and trimers all have significant enzymatic activity.  The higher the order of the oligomer, the better its enzymatic activity is.<ref name="liu01"/>  The pentamers, though their structure is not known, have shown the greatest enzymatic activity.  Though the high order oligomers are better enzymes, they are also degraded to their subunits faster.  The trimer will degrade to a dimer which will eventually degrade to a monomer.
+The monomers, dimers, and trimers all have significant enzymatic activity.  The higher the order of the oligomer, the higher its enzymatic activity.<ref name="liu01"/>  The pentamers, though their structure is not known, have shown the highest enzymatic activity.  Though the higher order oligomers are better enzymes, they are also degraded faster, where for instance the trimer will degrade to a dimer which will eventually degrade to a monomer.
-The major dimer is more active than the minor dimer, while the minor trimer is more active than the major trimer.<ref name="liu01"/>  It has been shown that the smaller the distance between two active sites, the greater the enzymatic activity on dsRNA.  The higher ordered oligomers are typically more tightly packed which would decrease the distance between active sites, and make them more active.<ref name="liu01"/>  Liu et. al. also predicts taht teh twisted orientation of the dimers and trimers allows for the destabilization of dsRNA.  Because the monomer does not have a twisted structure, it is not able to destabilize dsRNA.<ref name="liu01"/>
+The higher activity toward dsRNA is related to shorter distances between active sites.  The higher ordered oligomers are typically more tightly packed which would decrease the distance between active sites, and make them more active.<ref name="liu01"/>   For example, the major dimer is more active than the minor dimer, while the minor trimer is more active than the major trimer.<ref name="liu01"/>   Liu et. al. also predicts that the twisted orientation of the dimers and trimers allows for the destabilization of dsRNA.  Because the monomer does not have a twisted structure, it is not able to destabilize dsRNA.<ref name="liu01"/>
 ==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.
+[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 RNase 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"/>  Forty different proteins who form oligomers by 3D domain swapping have already been identified.<ref name="multimers">PMID:15104538</ref > As 3D domain swapping becomes more understood, it will offer insight to the amyloid formation in Alzheimer’s patients.
+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 antiparallel 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"/>  Forty different proteins who form oligomers by 3D domain swapping have already been identified.<ref name="multimers">PMID:15104538</ref > As 3D domain swapping becomes more understood, it will offer insight to the amyloid formation in Alzheimer’s patients.