View source for 3dzj


==Crystal structure of human CD38 extracellular domain E226Q mutant, NMN complex==
<StructureSection load='3dzj' size='340' side='right'caption='[[3dzj]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3dzj]] is a 2 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=3DZJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DZJ 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]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NMN:BETA-NICOTINAMIDE+RIBOSE+MONOPHOSPHATE'>NMN</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=3dzj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dzj OCA], [https://pdbe.org/3dzj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dzj RCSB], [https://www.ebi.ac.uk/pdbsum/3dzj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dzj 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/dz/3dzj_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=3dzj ConSurf].
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== Publication Abstract from PubMed ==
Enzymatic utilization of nicotinamide adenine dinucleotide (NAD) has increasingly been shown to have fundamental roles in gene regulation, signal transduction, and protein modification. Many of the processes require the cleavage of the nicotinamide moiety from the substrate and the formation of a reactive intermediate. Using X-ray crystallography, we show that human CD38, an NAD-utilizing enzyme, is capable of catalyzing the cleavage reactions through both covalent and noncovalent intermediates, depending on the substrate used. The covalent intermediate is resistant to further attack by nucleophiles, resulting in mechanism-based enzyme inactivation. The noncovalent intermediate is stabilized mainly through H-bond interactions, but appears to remain reactive. Our structural results favor the proposal of a noncovalent intermediate during normal enzymatic utilization of NAD by human CD38 and provide structural insights into the design of covalent and noncovalent inhibitors targeting NAD-utilization pathways.

Covalent and noncovalent intermediates of an NAD utilizing enzyme, human CD38.,Liu Q, Kriksunov IA, Jiang H, Graeff R, Lin H, Lee HC, Hao Q Chem Biol. 2008 Oct 20;15(10):1068-78. PMID:18940667<ref>PMID:18940667</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3dzj" 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: Jiang H]]
[[Category: Kriksunov IA]]
[[Category: Lee HC]]
[[Category: Lin H]]
[[Category: Liu Q]]