Sandbox Reserved 200: Difference between revisions

[[Image:2D_RNaseA.png|300px|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, tetramers, and pentamers based on the structure of the [http://www.proteopedia.org/wiki/index.php/Sandbox_Reserved_192 RNase A monomer].  Though there are many oligomers, the three-dimensional structure for only the major dimer, minor dimer, and minor trimer are known.  Unlike the monomers, all the 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.

<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 <scene name='Sandbox_Reserved_200/Major_dimer/11'>major</scene> and <scene name='Sandbox_Reserved_200/Minor_dimer/2'>minor</scene> dimer 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 major dimer 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 of 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>.

<scene name='Sandbox_Reserved_200/Minor_dimer/3'>hinge loop</scene> is the location where the two monomers connect acting like the hinge of a door.<ref name="liul"/>  The most important component of the hinge loops is Ala19.  <scene name='Sandbox_Reserved_200/Minor_dimer_hinge/1'>Ala19</scene> gives these hinges their flexibility.  This flexibility allows the dimers to adopt different orientations.<ref name="liu98"/>

Not only is the structure of the monomers conserved in the dimers, but the active is also conserved. <ref name="liu98"/>  The active site of both dimers contains His12, Lys41, and His119 residues.  The active sites are a composite of the monomer subunits containing His12 from one monomer and His119 form the other monomer.<ref name="liul"/>  During domain swapping, the active site is not disturbed, so the dimers are able to retain their enzymatic activity.   

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

The <scene name='Sandbox_Reserved_200/Minor_trimer/1'>minor trimer</scene> forms a cyclic propeller like shape.  It is 3D domain swapped at the C-terminus of the beta strand.<ref name="liu01"/>  No domain swapping a the N-terminus has been seen.  When the minor trimer dissociates, it forms a dimer and a monomer.  The minor and major dimer are both formed, but the major dimer is much more common.<ref name="liu01"/>     

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.

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.