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1z8l
From Proteopedia
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[[Image:1z8l.gif|left|200px]] | [[Image:1z8l.gif|left|200px]] | ||
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'''Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase''' | '''Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase''' | ||
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[[Category: Davis, M I.]] | [[Category: Davis, M I.]] | ||
[[Category: Thomas, L M.]] | [[Category: Thomas, L M.]] | ||
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| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 17:18:54 2008'' | |
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Revision as of 14:18, 3 May 2008
Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase
Overview
Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer cells and nonprostatic solid tumor neovasculature and is a target for anticancer imaging and therapeutic agents. PSMA acts as a glutamate carboxypeptidase (GCPII) on small molecule substrates, including folate, the anticancer drug methotrexate, and the neuropeptide N-acetyl-l-aspartyl-l-glutamate. Here we present the 3.5-A crystal structure of the PSMA ectodomain, which reveals a homodimer with structural similarity to transferrin receptor, a receptor for iron-loaded transferrin that lacks protease activity. Unlike transferrin receptor, the protease domain of PSMA contains a binuclear zinc site, catalytic residues, and a proposed substrate-binding arginine patch. Elucidation of the PSMA structure combined with docking studies and a proposed catalytic mechanism provides insight into the recognition of inhibitors and the natural substrate N-acetyl-l-aspartyl-l-glutamate. The PSMA structure will facilitate development of chemotherapeutics, cancer-imaging agents, and agents for treatment of neurological disorders.
About this Structure
1Z8L is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase., Davis MI, Bennett MJ, Thomas LM, Bjorkman PJ, Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):5981-6. Epub 2005 Apr 18. PMID:15837926 Page seeded by OCA on Sat May 3 17:18:54 2008
