We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

2pgl

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:2pgl.gif|left|200px]]
+
{{Seed}}
 +
[[Image:2pgl.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2pgl| PDB=2pgl | SCENE= }}
{{STRUCTURE_2pgl| PDB=2pgl | SCENE= }}
-
'''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
 +
(as it appears on PubMed at http://www.pubmed.gov), where 17591784 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_17591784}}
==About this Structure==
==About this Structure==
Line 33: Line 37:
[[Category: Substrate analog binding]]
[[Category: Substrate analog binding]]
[[Category: The catalytic pocket]]
[[Category: The catalytic pocket]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 13:04:18 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 18:37:25 2008''

Revision as of 15:37, 27 July 2008

Image:2pgl.png

Template:STRUCTURE 2pgl

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

Template:ABSTRACT PUBMED 17591784

About this Structure

2PGL 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 Jul 27 18:37:25 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2pgl"
Personal tools