2i67: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:2i67.gif|left|200px]]
- {{Structure
+==Structural Basis for the Mechanistic Understanding Human CD38 Controlled Multiple Catalysis==
-|PDB= 2i67 |SIZE=350|CAPTION= <scene name='initialview01'>2i67</scene>, resolution 1.71&Aring;
+<StructureSection load='2i67' size='340' side='right'caption='[[2i67]], [[Resolution|resolution]] 1.71&Aring;' scene=''>
-|SITE=
+== Structural highlights ==
-|LIGAND= <scene name='pdbligand=APR:ADENOSINE-5-DIPHOSPHORIBOSE'>APR</scene>
+<table><tr><td colspan='2'>[[2i67]] 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=2I67 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I67 FirstGlance]. <br>
-|ACTIVITY= [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]
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.71&#8491;</td></tr>
-|GENE= CD38 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=APR:ADENOSINE-5-DIPHOSPHORIBOSE'>APR</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=2i67 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i67 OCA], [https://pdbe.org/2i67 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i67 RCSB], [https://www.ebi.ac.uk/pdbsum/2i67 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i67 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/i6/2i67_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=2i67 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The enzymatic cleavage of the nicotinamide-glycosidic bond on nicotinamide adenine dinucleotide (NAD(+)) has been proposed to go through an oxocarbenium ion-like transition state. Because of the instability of the ionic intermediate, there has been no structural report on such a transient reactive species. Human CD38 is an ectoenzyme that can use NAD(+) to synthesize two calcium-mobilizing molecules. By using NAD(+) and a surrogate substrate, NGD(+), we captured and determined crystal structures of the enzyme complexed with an intermediate, a substrate, and a product along the reaction pathway. Our results showed that the intermediate is stabilized by polar interactions with the catalytic residue Glu(226) rather than by a covalent linkage. The polar interactions between Glu(226) and the substrate 2',3'-OH groups are essential for initiating catalysis. Ser(193) was demonstrated to have a regulative role during catalysis and is likely to be involved in intermediate stabilization. In addition, a product inhibition effect by ADP-ribose (through the reorientation of the product) or GDP-ribose (through the formation of a covalently linked GDP-ribose dimer) was observed. These structural data provide insights into the understanding of multiple catalysis and clues for drug design.
-'''Structural Basis for the Mechanistic Understanding Human CD38 Controlled Multiple Catalysis'''
+Structural basis for the mechanistic understanding of human CD38-controlled multiple catalysis.,Liu Q, Kriksunov IA, Graeff R, Munshi C, Lee HC, Hao Q J Biol Chem. 2006 Oct 27;281(43):32861-9. Epub 2006 Sep 2. PMID:16951430<ref>PMID:16951430</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2i67" style="background-color:#fffaf0;"></div>
-==Overview==
+==See Also==
-The enzymatic cleavage of the nicotinamide-glycosidic bond on nicotinamide adenine dinucleotide (NAD(+)) has been proposed to go through an oxocarbenium ion-like transition state. Because of the instability of the ionic intermediate, there has been no structural report on such a transient reactive species. Human CD38 is an ectoenzyme that can use NAD(+) to synthesize two calcium-mobilizing molecules. By using NAD(+) and a surrogate substrate, NGD(+), we captured and determined crystal structures of the enzyme complexed with an intermediate, a substrate, and a product along the reaction pathway. Our results showed that the intermediate is stabilized by polar interactions with the catalytic residue Glu(226) rather than by a covalent linkage. The polar interactions between Glu(226) and the substrate 2',3'-OH groups are essential for initiating catalysis. Ser(193) was demonstrated to have a regulative role during catalysis and is likely to be involved in intermediate stabilization. In addition, a product inhibition effect by ADP-ribose (through the reorientation of the product) or GDP-ribose (through the formation of a covalently linked GDP-ribose dimer) was observed. These structural data provide insights into the understanding of multiple catalysis and clues for drug design.
+*[[Cluster of Differentiation CD38|Cluster of Differentiation CD38]]
+== References ==
-==About this Structure==
+<references/>
-I67 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I67 OCA].
+__TOC__
+</StructureSection>
-==Reference==
-Structural basis for the mechanistic understanding of human CD38-controlled multiple catalysis., Liu Q, Kriksunov IA, Graeff R, Munshi C, Lee HC, Hao Q, J Biol Chem. 2006 Oct 27;281(43):32861-9. Epub 2006 Sep 2. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16951430 16951430]
 [[Category: Homo sapiens]]
-[[Category: NAD(+) nucleosidase]]
+[[Category: Large Structures]]
-[[Category: Single protein]]
+[[Category: Graeff R]]
-[[Category: Graeff, R.]]
+[[Category: Hao Q]]
-[[Category: Hao, Q.]]
+[[Category: Kriksunov IA]]
-[[Category: Kriksunov, I A.]]
+[[Category: Lee HC]]
-[[Category: Lee, H C.]]
+[[Category: Liu Q]]
-[[Category: Liu, Q.]]
+[[Category: Munshi C]]
-[[Category: Munshi, C.]]
-[[Category: APR]]
-[[Category: reaction intermediate]]
-[[Category: reaction product]]
-[[Category: the catalytic pocket]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:25:56 2008''