View source for 3f6y


==Conformational Closure of the Catalytic Site of Human CD38 Induced by Calcium==
<StructureSection load='3f6y' size='340' side='right'caption='[[3f6y]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3f6y]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F6Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F6Y FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.45&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3f6y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f6y OCA], [https://pdbe.org/3f6y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f6y RCSB], [https://www.ebi.ac.uk/pdbsum/3f6y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f6y ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CD38_HUMAN CD38_HUMAN] Synthesizes cyclic ADP-ribose, a second messenger for glucose-induced insulin secretion. Also has cADPr hydrolase activity. Also moonlights as a receptor in cells of the immune system.
== 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/f6/3f6y_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=3f6y ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
First identified on the surface of lymphoids as a type II transmembrane protein, CD38 has now been established to have dual functions not only as a receptor but also as a multifunctional enzyme,catalyzing the synthesis of and hydrolysis of a general calcium messenger molecule, cyclic ADP-ribose(cADPR). The receptorial functions of CD38 include the induction of cell adhesion, differentiation,apoptosis, and cytokine production upon antibody ligation. Here we determined the crystal structure of calcium-loaded human CD38 at 1.45 A resolution which reveals that CD38 undergoes dramatic structural changes to an inhibited conformation in the presence of calcium. The structural changes are highly localized and occur in only two regions. The first region is part of the active site and consists of residues 121-141.In the presence of calcium, W125 moves 5 A into the active site and forms hydrophobic interactions with W189. The movement closes the active site pocket and reduces entry of substrates, resulting in inhibition of the enzymatic activity. The structural role of calcium in inducing these conformational changes is readily visualized in the crystal structure. The other region that undergoes calcium-induced changes is at the receptor region, where a highly ordered helix is unraveled to a random coil. The results suggest a novel conformational coupling mechanism, whereby protein interaction targeted at the receptor region can effectively regulate the enzymatic activity of CD38.

Conformational Closure of the Catalytic Site of Human CD38 Induced by Calcium.,Liu Q, Graeff R, Kriksunov IA, Lam CM, Lee HC, Hao Q Biochemistry. 2008 Dec 30;47(52):13966-73. PMID:19117080<ref>PMID:19117080</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3f6y" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cluster of Differentiation CD38|Cluster of Differentiation CD38]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Graeff R]]
[[Category: Hao Q]]
[[Category: Kriksunov IA]]
[[Category: Lam CMC]]
[[Category: Lee HC]]
[[Category: Liu Q]]