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2c6g

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{{STRUCTURE_2c6g| PDB=2c6g | SCENE= }}
{{STRUCTURE_2c6g| PDB=2c6g | SCENE= }}
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'''MEMBRANE-BOUND GLUTAMATE CARBOXYPEPTIDASE II (GCPII) WITH BOUND GLUTAMATE'''
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===MEMBRANE-BOUND GLUTAMATE CARBOXYPEPTIDASE II (GCPII) WITH BOUND GLUTAMATE===
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==Overview==
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Membrane-bound glutamate carboxypeptidase II (GCPII) is a zinc metalloenzyme that catalyzes the hydrolysis of the neurotransmitter N-acetyl-L-aspartyl-L-glutamate (NAAG) to N-acetyl-L-aspartate and L-glutamate (which is itself a neurotransmitter). Potent and selective GCPII inhibitors have been shown to decrease brain glutamate and provide neuroprotection in preclinical models of stroke, amyotrophic lateral sclerosis, and neuropathic pain. Here, we report crystal structures of the extracellular part of GCPII in complex with both potent and weak inhibitors and with glutamate, the product of the enzyme's hydrolysis reaction, at 2.0, 2.4, and 2.2 A resolution, respectively. GCPII folds into three domains: protease-like, apical, and C-terminal. All three participate in substrate binding, with two of them directly involved in C-terminal glutamate recognition. One of the carbohydrate moieties of the enzyme is essential for homodimer formation of GCPII. The three-dimensional structures presented here reveal an induced-fit substrate-binding mode of this key enzyme and provide essential information for the design of GCPII inhibitors useful in the treatment of neuronal diseases and prostate cancer.
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{{ABSTRACT_PUBMED_16467855}}
==About this Structure==
==About this Structure==
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[[Category: Transmembrane]]
[[Category: Transmembrane]]
[[Category: Zinc]]
[[Category: Zinc]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 21:19:52 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 14:24:24 2008''

Revision as of 11:24, 27 July 2008

Image:2c6g.png

Template:STRUCTURE 2c6g

MEMBRANE-BOUND GLUTAMATE CARBOXYPEPTIDASE II (GCPII) WITH BOUND GLUTAMATE

Template:ABSTRACT PUBMED 16467855

About this Structure

2C6G is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure of glutamate carboxypeptidase II, a drug target in neuronal damage and prostate cancer., Mesters JR, Barinka C, Li W, Tsukamoto T, Majer P, Slusher BS, Konvalinka J, Hilgenfeld R, EMBO J. 2006 Mar 22;25(6):1375-84. Epub 2006 Feb 9. PMID:16467855

Page seeded by OCA on Sun Jul 27 14:24:24 2008

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