1z8l
From Proteopedia
|
Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase
Contents |
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.
Disease
Known diseases associated with this structure: Myocardial infarcation, susceptibility to OMIM:[602855]
About this Structure
1Z8L is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Glutamate carboxypeptidase II, with EC number 3.4.17.21 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 Thu Feb 21 16:13:07 2008
