2xej: Difference between revisions

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-{{Seed}}
-[[Image:2xej.jpg|left|200px]]
-<!--
+==Human glutamate carboxypeptidase II in complex with ARM-M4, urea- based inhibitor==
-The line below this paragraph, containing "STRUCTURE_2xej", creates the "Structure Box" on the page.
+<StructureSection load='2xej' size='340' side='right'caption='[[2xej]], [[Resolution|resolution]] 1.78&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2xej]] 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=2XEJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XEJ FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.78&#8491;</td></tr>
--->
+<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=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=OKD:N-({(1S)-1-CARBOXY-5-[4-(2,5,8,11,14-PENTAOXAPENTADEC-1-YL)-1H-1,2,3-TRIAZOL-1-YL]PENTYL}CARBAMOYL)-L-GLUTAMIC+ACID'>OKD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-{{STRUCTURE_2xej|  PDB=2xej  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2xej FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xej OCA], [https://pdbe.org/2xej PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xej RCSB], [https://www.ebi.ac.uk/pdbsum/2xej PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xej ProSAT]</span></td></tr>
+</table>
+== Function ==
+[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.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xe/2xej_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=2xej ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+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.
-===HUMAN GLUTAMATE CARBOXYPEPTIDASE II IN COMPLEX WITH ARM-M4, UREA-BASED INHIBITOR===
+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>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2xej" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_20726553}}, adds the Publication Abstract to the page
+*[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 20726553 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_20726553}}
+__TOC__
+</StructureSection>
-==About this Structure==
-XEJ is a 1 chain structure 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=2XEJ OCA].
-==Reference==
-<ref group="xtra">PMID:20726553</ref><references group="xtra"/>
-[[Category: Glutamate carboxypeptidase II]]
 [[Category: Homo sapiens]]
-[[Category: Barinka, C.]]
+[[Category: Large Structures]]
-[[Category: Cocleaza, A.]]
+[[Category: Barinka C]]
-[[Category: Jorgensen, W L.]]
+[[Category: Cocleaza A]]
-[[Category: Lubkowski, J.]]
+[[Category: Jorgensen WL]]
-[[Category: Michel, J.]]
+[[Category: Lubkowski J]]
-[[Category: Murelli, R.]]
+[[Category: Michel J]]
-[[Category: Spiegel, D A.]]
+[[Category: Murelli R]]
-[[Category: Zhang, A X.]]
+[[Category: Spiegel DA]]
-[[Category: Hydrolase]]
+[[Category: Zhang AX]]
-[[Category: Metallopeptidase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Sep 10 13:54:03 2010''