2jbj

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[[Image:2jbj.gif|left|200px]]<br /><applet load="2jbj" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2jbj, resolution 2.19&Aring;" />
 
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'''MEMBRANE-BOUND GLUTAMATE CARBOXYPEPTIDASE II (GCPII) IN COMPLEX WITH 2-PMPA (2-PHOSPHONOMETHYL-PENTANEDIOIC ACID)'''<br />
 
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==Overview==
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==membrane-bound glutamate carboxypeptidase II (GCPII) in complex with 2-PMPA (2-phosphonoMethyl-pentanedioic acid)==
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Human glutamate carboxypeptidase II (GCPII) occurs in the central nervous, system as well as in human prostate (where it is called prostate-specific, membrane antigen; PSMA). Inhibitors of the enzyme have been shown to, provide neuroprotection, but may also be useful for the detection, imaging, and treatment of prostate cancer. Crystal structures were determined of, the extracellular part of GCPII (amino-acid residues 44-750) in complex, with two potent inhibitors, quisqualate and 2-PMPA (the strongest GCPII, inhibitor to date), at resolutions of 3.0 and 2.2 A, respectively. In, addition, models were constructed for binding of the inhibitors, willardiine, homoibotenate, L-2-amino-4-phosphonobutanoic acid and, L-serine-O-sulfate to the S1' site of the enzyme. The common denominator, for high-affinity binding to the S1' site is the formation of two strong, salt bridges.
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<StructureSection load='2jbj' size='340' side='right'caption='[[2jbj]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2jbj]] is a 1 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=2JBJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JBJ 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]] 2.19&#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=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=G88:(2S)-2-(PHOSPHONOMETHYL)PENTANEDIOIC+ACID'>G88</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=2jbj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jbj OCA], [https://pdbe.org/2jbj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jbj RCSB], [https://www.ebi.ac.uk/pdbsum/2jbj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jbj 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/jb/2jbj_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2jbj 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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Human glutamate carboxypeptidase II (GCPII) occurs in the central nervous system as well as in human prostate (where it is called prostate-specific membrane antigen; PSMA). Inhibitors of the enzyme have been shown to provide neuroprotection, but may also be useful for the detection, imaging and treatment of prostate cancer. Crystal structures were determined of the extracellular part of GCPII (amino-acid residues 44-750) in complex with two potent inhibitors, quisqualate and 2-PMPA (the strongest GCPII inhibitor to date), at resolutions of 3.0 and 2.2 A, respectively. In addition, models were constructed for binding of the inhibitors willardiine, homoibotenate, L-2-amino-4-phosphonobutanoic acid and L-serine-O-sulfate to the S1' site of the enzyme. The common denominator for high-affinity binding to the S1' site is the formation of two strong salt bridges.
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==Disease==
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Human glutamate carboxypeptidase II inhibition: structures of GCPII in complex with two potent inhibitors, quisqualate and 2-PMPA.,Mesters JR, Henning K, Hilgenfeld R Acta Crystallogr D Biol Crystallogr. 2007 Apr;63(Pt 4):508-13. Epub 2007, Mar 16. PMID:17372356<ref>PMID:17372356</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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2JBJ 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:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC ION'>ZN</scene>, <scene name='pdbligand=CA:CALCIUM ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE ION'>CL</scene> and <scene name='pdbligand=G88:(2S)-2-(PHOSPHONOMETHYL)PENTANEDIOIC ACID'>G88</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] Known structural/functional Sites: <scene name='pdbsite=AC1:Zn Binding Site For Chain A'>AC1</scene>, <scene name='pdbsite=AC2:Zn Binding Site For Chain A'>AC2</scene>, <scene name='pdbsite=AC3:Ca Binding Site For Chain A'>AC3</scene>, <scene name='pdbsite=AC4:Cl Binding Site For Chain A'>AC4</scene>, <scene name='pdbsite=AC5:Nag Binding Site For Chain A'>AC5</scene>, <scene name='pdbsite=AC6:Nag Binding Site For Chain A'>AC6</scene>, <scene name='pdbsite=AC7:Nag Binding Site For Chain A'>AC7</scene>, <scene name='pdbsite=AC8:Nag Binding Site For Chain A'>AC8</scene>, <scene name='pdbsite=BC1:Nag Binding Site For Chain A'>BC1</scene>, <scene name='pdbsite=BC2:Nag Binding Site For Chain A'>BC2</scene>, <scene name='pdbsite=BC3:Nag Binding Site For Chain A'>BC3</scene>, <scene name='pdbsite=BC4:Nag Binding Site For Chain A'>BC4</scene>, <scene name='pdbsite=BC5:Nag Binding Site For Chain A'>BC5</scene>, <scene name='pdbsite=BC6:Nag Binding Site For Chain A'>BC6</scene>, <scene name='pdbsite=BC7:Bma Binding Site For Chain A'>BC7</scene>, <scene name='pdbsite=BC8:Man Binding Site For Chain A'>BC8</scene> and <scene name='pdbsite=BC9:G88 Binding Site For Chain A'>BC9</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2JBJ OCA].
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</div>
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<div class="pdbe-citations 2jbj" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Human glutamate carboxypeptidase II inhibition: structures of GCPII in complex with two potent inhibitors, quisqualate and 2-PMPA., Mesters JR, Henning K, Hilgenfeld R, Acta Crystallogr D Biol Crystallogr. 2007 Apr;63(Pt 4):508-13. Epub 2007, Mar 16. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17372356 17372356]
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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: Henning, K.]]
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[[Category: Henning K]]
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[[Category: Hilgenfeld, R.]]
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[[Category: Hilgenfeld R]]
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[[Category: Mesters, J.R.]]
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[[Category: Mesters JR]]
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[[Category: CA]]
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[[Category: CL]]
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[[Category: G88]]
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[[Category: NAG]]
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[[Category: ZN]]
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[[Category: alternative splicin]]
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[[Category: alternative splicing]]
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[[Category: antigen]]
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[[Category: carboxypeptidase]]
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[[Category: dipeptidase]]
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[[Category: glycoprotein]]
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[[Category: hydrolase]]
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[[Category: membrane]]
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[[Category: metal- binding]]
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[[Category: metal-binding]]
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[[Category: metalloprotease]]
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[[Category: multifunctional enzyme]]
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[[Category: naaladase]]
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[[Category: neurodegenerative disease]]
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[[Category: peptidase]]
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[[Category: polymorphism]]
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[[Category: prostate cancer]]
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[[Category: protease]]
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[[Category: psma]]
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[[Category: signal-anchor]]
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[[Category: transmembrane]]
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[[Category: zinc]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Dec 19 13:19:04 2007''
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Current revision

membrane-bound glutamate carboxypeptidase II (GCPII) in complex with 2-PMPA (2-phosphonoMethyl-pentanedioic acid)

PDB ID 2jbj

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