View source for 2a72


==Structure of the regulator of G-protein signaling domain of RGS7==
<StructureSection load='2a72' size='340' side='right'caption='[[2a72]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2a72]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A72 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2A72 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2a72 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a72 OCA], [http://pdbe.org/2a72 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2a72 RCSB], [http://www.ebi.ac.uk/pdbsum/2a72 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2a72 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/RGS7_HUMAN RGS7_HUMAN]] Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Activity on G(o)-alpha is specifically enhanced by the RGS6/GNG5 dimer. May play a role in synaptic vesicle exocytosis. May play important role in the rapid regulation of neuronal excitability and the cellular responses to short-lived stimulations (By similarity). 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a7/2a72_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2a72 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Regulator of G protein signaling (RGS) proteins accelerate GTP hydrolysis by Galpha subunits and thus facilitate termination of signaling initiated by G protein-coupled receptors (GPCRs). RGS proteins hold great promise as disease intervention points, given their signature role as negative regulators of GPCRs-receptors to which the largest fraction of approved medications are currently directed. RGS proteins share a hallmark RGS domain that interacts most avidly with Galpha when in its transition state for GTP hydrolysis; by binding and stabilizing switch regions I and II of Galpha, RGS domain binding consequently accelerates Galpha-mediated GTP hydrolysis. The human genome encodes more than three dozen RGS domain-containing proteins with varied Galpha substrate specificities. To facilitate their exploitation as drug-discovery targets, we have taken a systematic structural biology approach toward cataloging the structural diversity present among RGS domains and identifying molecular determinants of their differential Galpha selectivities. Here, we determined 14 structures derived from NMR and x-ray crystallography of members of the R4, R7, R12, and RZ subfamilies of RGS proteins, including 10 uncomplexed RGS domains and 4 RGS domain/Galpha complexes. Heterogeneity observed in the structural architecture of the RGS domain, as well as in engagement of switch III and the all-helical domain of the Galpha substrate, suggests that unique structural determinants specific to particular RGS protein/Galpha pairings exist and could be used to achieve selective inhibition by small molecules.

Structural diversity in the RGS domain and its interaction with heterotrimeric G protein alpha-subunits.,Soundararajan M, Willard FS, Kimple AJ, Turnbull AP, Ball LJ, Schoch GA, Gileadi C, Fedorov OY, Dowler EF, Higman VA, Hutsell SQ, Sundstrom M, Doyle DA, Siderovski DP Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6457-62. Epub 2008 Apr 23. PMID:18434541<ref>PMID:18434541</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2a72" style="background-color:#fffaf0;"></div>

==See Also==
*[[Regulator of G-protein signaling 3D structures|Regulator of G-protein signaling 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Arrowsmith, C]]
[[Category: Debreczeni, J]]
[[Category: Delft, F von]]
[[Category: Doyle, D A]]
[[Category: Edwards, A]]
[[Category: Elkins, J M]]
[[Category: Gileadi, O]]
[[Category: Johansson, C]]
[[Category: Phillips, C]]
[[Category: Structural genomic]]
[[Category: Schoch, G A]]
[[Category: Smee, C]]
[[Category: Sundstrom, M]]
[[Category: Human rgs7]]
[[Category: Regulator of g-protein signaling 7]]
[[Category: Sgc]]
[[Category: Signaling protein]]