3roq: Difference between revisions
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==Crystal structure of human CD38 in complex with compound CZ-46== | ==Crystal structure of human CD38 in complex with compound CZ-46== | ||
<StructureSection load='3roq' size='340' side='right' caption='[[3roq]], [[Resolution|resolution]] 2.10Å' scene=''> | <StructureSection load='3roq' size='340' side='right' caption='[[3roq]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3roq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3roq]] 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=3ROQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ROQ FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=46Z:(2R,3R,4S,5S)-4-FLUORO-3,5-DIHYDROXYTETRAHYDROFURAN-2-YL+2-PHENYLETHYL+HYDROGEN+(S)-PHOSPHATE'>46Z</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=46Z:(2R,3R,4S,5S)-4-FLUORO-3,5-DIHYDROXYTETRAHYDROFURAN-2-YL+2-PHENYLETHYL+HYDROGEN+(S)-PHOSPHATE'>46Z</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1yh3|1yh3]], [[3rok|3rok]], [[3rom|3rom]], [[3rop|3rop]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1yh3|1yh3]], [[3rok|3rok]], [[3rom|3rom]], [[3rop|3rop]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CD38 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CD38 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_nucleosidase NAD(+) nucleosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.5 3.2.2.5] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_nucleosidase NAD(+) nucleosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.5 3.2.2.5] </span></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=3roq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3roq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3roq RCSB], [http://www.ebi.ac.uk/pdbsum/3roq PDBsum]</span></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=3roq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3roq OCA], [http://pdbe.org/3roq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3roq RCSB], [http://www.ebi.ac.uk/pdbsum/3roq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3roq ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3roq" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Human]] | ||
[[Category: Hao, Q]] | [[Category: Hao, Q]] | ||
[[Category: Lee, H C]] | [[Category: Lee, H C]] | ||
Revision as of 13:36, 5 August 2016
Crystal structure of human CD38 in complex with compound CZ-46Crystal structure of human CD38 in complex with compound CZ-46
Structural highlights
Function[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. Publication Abstract from PubMedCD38 is a signaling enzyme responsible for catalyzing the synthesis of cyclic ADP ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate; both are universal Ca(2+) messenger molecules. Ablation of the CD38 gene in mice causes multiple physiological defects, including impaired oxytocin release, that result in altered social behavior. A series of catalysis-based inhibitors of CD38 were designed and synthesized, starting with arabinosyl-2'-fluoro-2'-deoxynicotinamide mononucleotide. Structure-function relationships were analyzed to assess the structural determinants important for inhibiting the NADase activity of CD38. X-ray crystallography was used to reveal the covalent intermediates that were formed with the catalytic residue, Glu226. Metabolically stable analogues that were resistant to inactivation by phosphatase and esterase were synthesized and shown to be effective in inhibiting intracellular cADPR production in human HL-60 cells during induction of differentiation by retinoic acid. The inhibition was species-independent, and the analogues were similarly effective in blocking the cyclization reaction of CD38 in rat ventricular tissue extracts, as well as inhibiting the alpha-agonist-induced constriction in rat mesentery arteries. These compounds thus represent the first generally applicable and catalysis-based inhibitors of the Ca(2+) signaling function of CD38. Catalysis-Based Inhibitors of the Calcium Signaling Function of CD38.,Kwong AK, Chen Z, Zhang H, Leung FP, Lam CM, Ting KY, Zhang L, Hao Q, Zhang LH, Lee HC Biochemistry. 2011 Dec 14. PMID:22142305[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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