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1z8l

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(New page: 200px<br /> <applet load="1z8l" size="450" color="white" frame="true" align="right" spinBox="true" caption="1z8l, resolution 3.5&Aring;" /> '''Crystal structure of...)
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[[Image:1z8l.gif|left|200px]]<br />
 
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<applet load="1z8l" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1z8l, resolution 3.5&Aring;" />
 
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'''Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase'''<br />
 
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==Overview==
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==Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase==
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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.
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<StructureSection load='1z8l' size='340' side='right'caption='[[1z8l]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1z8l]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z8L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Z8L FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.5&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1z8l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z8l OCA], [https://pdbe.org/1z8l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1z8l RCSB], [https://www.ebi.ac.uk/pdbsum/1z8l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1z8l ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/FOLH1_HUMAN FOLH1_HUMAN] Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate. In the brain, modulates excitatory neurotransmission through the hydrolysis of the neuropeptide, N-aceylaspartylglutamate (NAAG), thereby releasing glutamate. Isoform PSM-4 and isoform PSM-5 would appear to be physiologically irrelevant. Involved in prostate tumor progression. Also exhibits a dipeptidyl-peptidase IV type activity. In vitro, cleaves Gly-Pro-AMC.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z8/1z8l_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1z8l ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==Disease==
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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<ref>PMID:15837926</ref>
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Known diseases associated with this structure: Myocardial infarcation, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602855 602855]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1Z8L OCA].
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</div>
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<div class="pdbe-citations 1z8l" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15837926 15837926]
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*[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]]
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[[Category: Glutamate carboxypeptidase II]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Bennett, M.J.]]
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[[Category: Bennett MJ]]
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[[Category: Bjorkman, P.J.]]
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[[Category: Bjorkman PJ]]
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[[Category: Davis, M.I.]]
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[[Category: Davis MI]]
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[[Category: Thomas, L.M.]]
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[[Category: Thomas LM]]
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[[Category: NAG]]
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[[Category: ZN]]
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[[Category: dimeric protein with three domains of type a+b]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:31:08 2007''
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Current revision

Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase

PDB ID 1z8l

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