6i6z: Difference between revisions

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 ==Crystal structure of the human CARBOXYPEPTIDASE A1 in complex with the PHOSPHINIC INHIBITOR Acetyl-Tyr-Ala-Y(PO2CH2)-homoPhe-OH==
-<StructureSection load='6i6z' size='340' side='right' caption='[[6i6z]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
+<StructureSection load='6i6z' size='340' side='right'caption='[[6i6z]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6i6z]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I6Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I6Z FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6i6z]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4uef 4uef]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I6Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I6Z FirstGlance]. <br>
-</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TJE:(2S)-2-{[(S)-{(1R)-1-[(N-ACETYL-L-TYROSYL)AMINO]ETHYL}(HYDROXY)PHOSPHORYL]METHYL}-4-PHENYLBUTANOIC+ACID'>TJE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.72&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Carboxypeptidase_A Carboxypeptidase A], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.17.1 3.4.17.1] </span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TJE:(2S)-2-{[(S)-{(1R)-1-[(N-ACETYL-L-TYROSYL)AMINO]ETHYL}(HYDROXY)PHOSPHORYL]METHYL}-4-PHENYLBUTANOIC+ACID'>TJE</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6i6z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i6z OCA], [http://pdbe.org/6i6z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i6z RCSB], [http://www.ebi.ac.uk/pdbsum/6i6z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i6z ProSAT]</span></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=6i6z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i6z OCA], [https://pdbe.org/6i6z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i6z RCSB], [https://www.ebi.ac.uk/pdbsum/6i6z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i6z ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/CBPA1_HUMAN CBPA1_HUMAN]] Carboxypeptidase that catalyzes the release of a C-terminal amino acid, but has little or no action with -Asp, -Glu, -Arg, -Lys or -Pro.<ref>PMID:8806703</ref>
+[https://www.uniprot.org/uniprot/CBPA1_HUMAN CBPA1_HUMAN] Carboxypeptidase that catalyzes the release of a C-terminal amino acid, but has little or no action with -Asp, -Glu, -Arg, -Lys or -Pro.<ref>PMID:8806703</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Metallocarboxypeptidases (MCPs) of the M14 family are Zn(2+)-dependent exoproteases present in almost every tissue or fluid in mammals. These enzymes perform a large variety of physiological functions and are involved in several pathologies, such as pancreatic diseases, inflammation, fibrinolysis, and cancer. Here, we describe the synthesis and functional/structural characterization of a series of reversible tight-binding phosphinic pseudopeptide inhibitors that show high specificity and potency toward these proteases. Characterization of their inhibitory potential against a large variety of MCPs, combined with high-resolution crystal structures of three selected candidates in complex with human carboxypeptidase A (CPA)1, allowed to decipher the structural determinants governing selectivity for type-A of the M14A MCP family. Further, the phosphinic pseudopeptide framework was exploited to generate an optical probe selectively targeting human CPAs. The phosphinic pseudopeptides presented here constitute the first example of chemical probes useful to selectively report on type-A MCPs activity in complex media.
+Synthesis and Structural/Functional Characterization of Selective M14 Metallocarboxypeptidase Inhibitors Based on Phosphinic Pseudopeptide Scaffold: Implications on the Design of Specific Optical Probes.,Covaleda G, Gallego P, Vendrell J, Georgiadis D, Lorenzo J, Dive V, Aviles FX, Reverter D, Devel L J Med Chem. 2019 Feb 28;62(4):1917-1931. doi: 10.1021/acs.jmedchem.8b01465. Epub , 2019 Feb 13. PMID:30688452<ref>PMID:30688452</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6i6z" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Carboxypeptidase A]]
+[[Category: Homo sapiens]]
-[[Category: Gallego, P]]
+[[Category: Large Structures]]
-[[Category: Reverter, D]]
+[[Category: Gallego P]]
-[[Category: Hydrolase]]
+[[Category: Reverter D]]
-[[Category: Protease]]