1z8l
From Proteopedia
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| , resolution 3.5Å | |||||||
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| Ligands: | , , | ||||||
| Gene: | FOLH1, FOLH, NAALAD1, PSM, PSMA (Homo sapiens) | ||||||
| Activity: | Glutamate carboxypeptidase II, with EC number 3.4.17.21 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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
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