1Z8L
Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase
Summary for 1Z8L
| Entry DOI | 10.2210/pdb1z8l/pdb |
| Descriptor | Glutamate carboxypeptidase II, 2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total) |
| Functional Keywords | dimeric protein with three domains of type a+b, hydrolase |
| Biological source | Homo sapiens (human) |
| Cellular location | Cell membrane; Single-pass type II membrane protein. Isoform PSMA': Cytoplasm: Q04609 |
| Total number of polymer chains | 4 |
| Total formula weight | 324146.36 |
| Authors | Davis, M.I.,Bennett, M.J.,Thomas, L.M.,Bjorkman, P.J. (deposition date: 2005-03-30, release date: 2005-04-19, Last modification date: 2024-11-13) |
| Primary citation | Davis, M.I.,Bennett, M.J.,Thomas, L.M.,Bjorkman, P.J. Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase Proc.Natl.Acad.Sci.USA, 102:5981-5986, 2005 Cited by PubMed Abstract: 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. PubMed: 15837926DOI: 10.1073/pnas.0502101102 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.5 Å) |
Structure validation
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