2pgj

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[[Image:2pgj.gif|left|200px]]
[[Image:2pgj.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 2pgj |SIZE=350|CAPTION= <scene name='initialview01'>2pgj</scene>, resolution 1.71&Aring;
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The line below this paragraph, containing "STRUCTURE_2pgj", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=N1C:N1-CYCLIC+INOSINE+5&#39;-DIPHOSPHORIBOSE'>N1C</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <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>
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or leave the SCENE parameter empty for the default display.
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|GENE= CD38 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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-->
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|DOMAIN=
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{{STRUCTURE_2pgj| PDB=2pgj | SCENE= }}
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|RELATEDENTRY=[[2pgl|2PGL]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2pgj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pgj OCA], [http://www.ebi.ac.uk/pdbsum/2pgj PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2pgj RCSB]</span>
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}}
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'''Catalysis associated conformational changes revealed by human cd38 complexed with a non-hydrolyzable substrate analog'''
'''Catalysis associated conformational changes revealed by human cd38 complexed with a non-hydrolyzable substrate analog'''
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Catalysis-associated conformational changes revealed by human CD38 complexed with a non-hydrolyzable substrate analog., Liu Q, Kriksunov IA, Moreau C, Graeff R, Potter BV, Lee HC, Hao Q, J Biol Chem. 2007 Aug 24;282(34):24825-32. Epub 2007 Jun 25. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17591784 17591784]
Catalysis-associated conformational changes revealed by human CD38 complexed with a non-hydrolyzable substrate analog., Liu Q, Kriksunov IA, Moreau C, Graeff R, Potter BV, Lee HC, Hao Q, J Biol Chem. 2007 Aug 24;282(34):24825-32. Epub 2007 Jun 25. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17591784 17591784]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: NAD(+) nucleosidase]]
 
[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Graeff, R.]]
[[Category: Graeff, R.]]
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[[Category: Moreau, C.]]
[[Category: Moreau, C.]]
[[Category: Potter, B V.L.]]
[[Category: Potter, B V.L.]]
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[[Category: conformational changes of the active site]]
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[[Category: Conformational changes of the active site]]
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[[Category: substrate analog binding]]
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[[Category: Substrate analog binding]]
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[[Category: the catalytic pocket]]
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[[Category: The catalytic pocket]]
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[[Category: wild-type cd38 bound with n1-cidpr]]
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[[Category: Wild-type cd38 bound with n1-cidpr]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 13:04:14 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:35:39 2008''
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Revision as of 10:04, 4 May 2008

Image:2pgj.gif

Template:STRUCTURE 2pgj

Catalysis associated conformational changes revealed by human cd38 complexed with a non-hydrolyzable substrate analog


Overview

Cyclic ADP-ribose (cADPR) is a calcium mobilization messenger important for mediating a wide range of physiological functions. The endogenous levels of cADPR in mammalian tissues are primarily controlled by CD38, a multifunctional enzyme capable of both synthesizing and hydrolyzing cADPR. In this study, a novel non-hydrolyzable analog of cADPR, N1-cIDPR (N1-cyclic inosine diphosphate ribose), was utilized to elucidate the structural determinants involved in the hydrolysis of cADPR. N1-cIDPR inhibits CD38-catalyzed cADPR hydrolysis with an IC(50) of 0.26 mM. N1-cIDPR forms a complex with CD38 or its inactive mutant in which the catalytic residue Glu-226 is mutated. Both complexes have been determined by x-ray crystallography at 1.7 and 1.76 A resolution, respectively. The results show that N1-cIDPR forms two hydrogen bonds (2.61 and 2.64 A) with Glu-226, confirming our previously proposed model for cADPR catalysis. Structural analyses reveal that both the enzyme and substrate cADPR undergo catalysis-associated conformational changes. From the enzyme side, residues Glu-146, Asp-147, and Trp-125 work collaboratively to facilitate the formation of the Michaelis complex. From the substrate side, cADPR is found to change its conformation to fit into the active site until it reaches the catalytic residue. The binary CD38-cADPR model described here represents the most detailed description of the CD38-catalyzed hydrolysis of cADPR at atomic resolution. Our structural model should provide insights into the design of effective cADPR analogs.

About this Structure

2PGJ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Catalysis-associated conformational changes revealed by human CD38 complexed with a non-hydrolyzable substrate analog., Liu Q, Kriksunov IA, Moreau C, Graeff R, Potter BV, Lee HC, Hao Q, J Biol Chem. 2007 Aug 24;282(34):24825-32. Epub 2007 Jun 25. PMID:17591784 Page seeded by OCA on Sun May 4 13:04:14 2008

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