2afm: Difference between revisions

Revision as of 14:57, 27 July 2008

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File:2afm.png

Template:STRUCTURE 2afm

Crystal structure of human glutaminyl cyclase at pH 6.5Crystal structure of human glutaminyl cyclase at pH 6.5

Template:ABSTRACT PUBMED 16135565

About this StructureAbout this Structure

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

ReferenceReference

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

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OCA

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-'''Crystal structure of human glutaminyl cyclase at pH 6.5'''
+===Crystal structure of human glutaminyl cyclase at pH 6.5===
-==Overview==
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-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
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 ==About this Structure==
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 [[Category: Alpha-beta protein]]
 [[Category: Metalloprotein]]
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