2pgl: Difference between revisions

Revision as of 18:37, 27 July 2008

This article has been automatically seeded. Changes to this page should pertain to the PDB entry only and not to the protein or biomolecule in general.

File:2pgl.png

Template:STRUCTURE 2pgl

Catalysis associated conformational changes revealed by human CD38 complexed with a non-hydrolyzable substrate analogCatalysis associated conformational changes revealed by human CD38 complexed with a non-hydrolyzable substrate analog

Template:ABSTRACT PUBMED 17591784

About this StructureAbout this Structure

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

ReferenceReference

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

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OCA

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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===
-==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.
+The line below this paragraph, {{ABSTRACT_PUBMED_17591784}}, adds the Publication Abstract to the page
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+{{ABSTRACT_PUBMED_17591784}}
 ==About this Structure==
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 [[Category: Substrate analog binding]]
 [[Category: The catalytic pocket]]
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