text: Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase.
  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.
entities.id: T10 T11 T12 T13 T14 T15 T16 T17 T18 T19 T1 T20 T21 T22 T23 T24 T2 T3 T4 T5 T6 T7 T8 T9
entities.type: GENE-Y GENE-N GENE-Y GENE-Y GENE-N GENE-N GENE-Y GENE-N GENE-N GENE-N CHEMICAL GENE-Y GENE-Y GENE-Y GENE-Y GENE-N CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-Y
entities.text: PSMA glutamate carboxypeptidase GCPII PSMA PSMA ectodomain transferrin receptor transferrin protease transferrin receptor protease domain glutamate PSMA PSMA PSMA prostate-specific membrane antigen peptidase folate methotrexate N-acetyl-l-aspartyl-l-glutamate iron zinc arginine N-acetyl-l-aspartyl-l-glutamate Prostate-specific membrane antigen