1z8l: Difference between revisions
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New page: left|200px<br /> <applet load="1z8l" size="450" color="white" frame="true" align="right" spinBox="true" caption="1z8l, resolution 3.5Å" /> '''Crystal structure of... |
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[[Image:1z8l.gif|left|200px]]<br /> | [[Image:1z8l.gif|left|200px]]<br /><applet load="1z8l" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1z8l" size=" | |||
caption="1z8l, resolution 3.5Å" /> | caption="1z8l, resolution 3.5Å" /> | ||
'''Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase'''<br /> | '''Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase'''<br /> | ||
==Overview== | ==Overview== | ||
Prostate-specific membrane antigen (PSMA) is highly expressed in prostate | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1Z8L is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG and ZN as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glutamate_carboxypeptidase_II Glutamate carboxypeptidase II], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.21 3.4.17.21] Full crystallographic information is available from [http:// | 1Z8L is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene> and <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glutamate_carboxypeptidase_II Glutamate carboxypeptidase II], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.21 3.4.17.21] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z8L OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bennett, M | [[Category: Bennett, M J.]] | ||
[[Category: Bjorkman, P | [[Category: Bjorkman, P J.]] | ||
[[Category: Davis, M | [[Category: Davis, M I.]] | ||
[[Category: Thomas, L | [[Category: Thomas, L M.]] | ||
[[Category: NAG]] | [[Category: NAG]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
[[Category: dimeric protein with three domains of type a+b]] | [[Category: dimeric protein with three domains of type a+b]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:13:07 2008'' | ||
