2afx

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:2afx.gif|left|200px]]
+
{{Seed}}
 +
[[Image:2afx.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2afx| PDB=2afx | SCENE= }}
{{STRUCTURE_2afx| PDB=2afx | SCENE= }}
-
'''Crystal structure of human glutaminyl cyclase in complex with 1-benzylimidazole'''
+
===Crystal structure of human glutaminyl cyclase in complex with 1-benzylimidazole===
-
==Overview==
+
<!--
-
N-terminal pyroglutamate (pGlu) formation from its glutaminyl (or glutamyl) precursor is required in the maturation of numerous bioactive peptides. The aberrant formation of pGlu may be related to several pathological processes, such as osteoporosis and amyloidotic diseases. This N-terminal cyclization reaction, once thought to proceed spontaneously, is greatly facilitated by the enzyme glutaminyl cyclase (QC). To probe this important but poorly understood modification, we present here the structure of human QC in free form and bound to a substrate and three imidazole-derived inhibitors. The structure reveals an alpha/beta scaffold akin to that of two-zinc exopeptidases but with several insertions and deletions, particularly in the active-site region. The relatively closed active site displays alternate conformations due to the different indole orientations of Trp-207, resulting in two substrate (glutamine t-butyl ester)-binding modes. The single zinc ion in the active site is coordinated to three conserved residues and one water molecule, which is replaced by an imidazole nitrogen upon binding of the inhibitors. Together with structural and kinetic analyses of several active-site-mutant enzymes, a catalysis mechanism of the formation of protein N-terminal pGlu is proposed. Our results provide a structural basis for the rational design of inhibitors against QC-associated disorders.
+
The line below this paragraph, {{ABSTRACT_PUBMED_16135565}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 16135565 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_16135565}}
==About this Structure==
==About this Structure==
Line 30: Line 34:
[[Category: Alpha-beta protein]]
[[Category: Alpha-beta protein]]
[[Category: Metalloprotein]]
[[Category: Metalloprotein]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 19:00:14 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 07:48:19 2008''

Revision as of 04:48, 29 July 2008

Image:2afx.png

Template:STRUCTURE 2afx

Crystal structure of human glutaminyl cyclase in complex with 1-benzylimidazole

Template:ABSTRACT PUBMED 16135565

About this Structure

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

Reference

Crystal structures of human glutaminyl cyclase, an enzyme responsible for protein N-terminal pyroglutamate formation., Huang KF, Liu YL, Cheng WJ, Ko TP, Wang AH, Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13117-22. Epub 2005 Aug 31. PMID:16135565

Page seeded by OCA on Tue Jul 29 07:48:19 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

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