2xef

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[[Image:2xef.png|left|200px]]
 
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==Human glutamate carboxypeptidase II in complex with Antibody- Recruiting Molecule ARM-P8==
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The line below this paragraph, containing "STRUCTURE_2xef", creates the "Structure Box" on the page.
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<StructureSection load='2xef' size='340' side='right'caption='[[2xef]], [[Resolution|resolution]] 1.59&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2xef]] 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=2XEF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XEF FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 1.59&#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=AR8:N-{[(1S)-5-{4-[25-({2,4-BIS[HYDROXY(OXO)AMMONIO]PHENYL}AMINO)-2,5,8,11,14,17,20,23-OCTAOXAPENTACOS-1-YL]-1H-1,2,3-TRIAZOL-1-YL}-1-CARBOXYPENTYL]CARBAMOYL}-L-GLUTAMIC+ACID'>AR8</scene>, <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=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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{{STRUCTURE_2xef| PDB=2xef | SCENE= }}
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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=2xef FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xef OCA], [https://pdbe.org/2xef PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xef RCSB], [https://www.ebi.ac.uk/pdbsum/2xef PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xef 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/xe/2xef_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=2xef 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 a membrane-bound glutamate carboxypeptidase overexpressed in many forms of prostate cancer. Our laboratory has recently disclosed a class of small molecules, called ARM-Ps (antibody-recruiting molecule targeting prostate cancer) that are capable of enhancing antibody-mediated immune recognition of prostate cancer cells. Interestingly, during the course of these studies, we found ARM-Ps to exhibit extraordinarily high potencies toward PSMA, compared to previously reported inhibitors. Here, we report in-depth biochemical, crystallographic, and computational investigations which elucidate the origin of the observed affinity enhancement. These studies reveal a previously unreported arene-binding site on PSMA, which we believe participates in an aromatic stacking interaction with ARMs. Although this site is composed of only a few amino acid residues, it drastically enhances small molecule binding affinity. These results provide critical insights into the design of PSMA-targeted small molecules for prostate cancer diagnosis and treatment; more broadly, the presence of similar arene-binding sites throughout the proteome could prove widely enabling in the optimization of small molecule-protein interactions.
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===HUMAN GLUTAMATE CARBOXYPEPTIDASE II IN COMPLEX WITH ANTIBODY-RECRUITING MOLECULE ARM-P8===
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A remote arene-binding site on prostate specific membrane antigen revealed by antibody-recruiting small molecules.,Zhang AX, Murelli RP, Barinka C, Michel J, Cocleaza A, Jorgensen WL, Lubkowski J, Spiegel DA J Am Chem Soc. 2010 Sep 15;132(36):12711-6. PMID:20726553<ref>PMID:20726553</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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The line below this paragraph, {{ABSTRACT_PUBMED_20726553}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 2xef" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 20726553 is the PubMed ID number.
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{{ABSTRACT_PUBMED_20726553}}
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==About this Structure==
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[[2xef]] is a 1 chain structure of [[ABC transporter]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XEF OCA].
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==See Also==
==See Also==
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*[[ABC transporter]]
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*[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:020726553</ref><references group="xtra"/>
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__TOC__
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[[Category: Glutamate carboxypeptidase II]]
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Barinka, C.]]
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[[Category: Large Structures]]
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[[Category: Cocleaza, A.]]
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[[Category: Barinka C]]
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[[Category: Jorgensen, W L.]]
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[[Category: Cocleaza A]]
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[[Category: Lubkowski, J.]]
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[[Category: Jorgensen WL]]
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[[Category: Michel, J.]]
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[[Category: Lubkowski J]]
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[[Category: Murelli, R P.]]
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[[Category: Michel J]]
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[[Category: Spiegel, D A.]]
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[[Category: Murelli RP]]
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[[Category: Zhang, A X.]]
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[[Category: Spiegel DA]]
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[[Category: Hydrolase]]
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[[Category: Zhang AX]]
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[[Category: Metallopeptidase]]
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Current revision

Human glutamate carboxypeptidase II in complex with Antibody- Recruiting Molecule ARM-P8

PDB ID 2xef

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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