6rbc
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==X-ray structure of human glutamate carboxypeptidase II (GCPII) in complex with a inhibitor KB1157== | |
| + | <StructureSection load='6rbc' size='340' side='right'caption='[[6rbc]], [[Resolution|resolution]] 1.77Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6rbc]] 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=6RBC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RBC FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.77Å</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=JX5:(2~{S})-2-[[(2~{R})-2-[4-[(4-iodophenyl)carbonylamino]butanoylamino]-3-oxidanyl-3-oxidanylidene-propyl]carbamoylamino]pentanedioic+acid'>JX5</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> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6rbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rbc OCA], [https://pdbe.org/6rbc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rbc RCSB], [https://www.ebi.ac.uk/pdbsum/6rbc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rbc 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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Prostate-specific membrane antigen (PSMA) is an excellent biomarker for the early diagnosis of prostate cancer progression and metastasis. The most promising PSMA-targeted agents in the clinical phase are based on the Lys-urea-Glu motif, in which Lys and Glu are alpha-(l)-amino acids. In this study, we aimed to determine the effect of beta- and gamma-amino acids in the S1 pocket on the binding affinity for PSMA. We synthesized and evaluated the beta- and gamma-amino acid analogues with (S)- or (R)-configuration with keeping alpha-(l)-Glu as the S1'-binding pharmacophore. The structure-activity relationship studies identified that compound 13c, a beta-amino acid analogue with (R)-configuration, exhibited the most potent PSMA inhibitory activity with an IC50 value of 3.97 nM. The X-ray crystal structure of PSMA in complex with 13c provided a mechanistic basis for the stereochemical preference of PSMA, which can guide the development of future PSMA inhibitors. | ||
| - | + | Novel beta- and gamma-Amino Acid-Derived Inhibitors of Prostate-Specific Membrane Antigen.,Kim K, Kwon H, Barinka C, Motlova L, Nam S, Choi D, Ha H, Nam H, Son SH, Minn I, Pomper MG, Yang X, Kutil Z, Byun Y J Med Chem. 2020 Mar 26;63(6):3261-3273. doi: 10.1021/acs.jmedchem.9b02022. Epub , 2020 Mar 9. PMID:32097010<ref>PMID:32097010</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Barinka | + | <div class="pdbe-citations 6rbc" style="background-color:#fffaf0;"></div> |
| - | [[Category: Kutil | + | |
| + | ==See Also== | ||
| + | *[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Barinka C]] | ||
| + | [[Category: Kutil Z]] | ||
Current revision
X-ray structure of human glutamate carboxypeptidase II (GCPII) in complex with a inhibitor KB1157
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