5om9
From Proteopedia
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(New page: ==Crystal structure of the human CARBOXYPEPTIDASE A1 in complex with a thiirane mechanism-based inhibitor== <StructureSection load='5om9' size='340' side='right' caption='5om9, [[Reso...) |
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==Crystal structure of the human CARBOXYPEPTIDASE A1 in complex with a thiirane mechanism-based inhibitor== | ==Crystal structure of the human CARBOXYPEPTIDASE A1 in complex with a thiirane mechanism-based inhibitor== | ||
| - | <StructureSection load='5om9' size='340' side='right' caption='[[5om9]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='5om9' size='340' side='right'caption='[[5om9]], [[Resolution|resolution]] 1.80Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5om9]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OM9 OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5om9]] 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=4uf4 4uf4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OM9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OM9 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=O2S:(2~{R})-4-methyl-2-[(1~{S})-1-sulfanylethyl]pentanoic+acid'>O2S</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=O2S:(2~{R})-4-methyl-2-[(1~{S})-1-sulfanylethyl]pentanoic+acid'>O2S</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=5om9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5om9 OCA], [https://pdbe.org/5om9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5om9 RCSB], [https://www.ebi.ac.uk/pdbsum/5om9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5om9 ProSAT]</span></td></tr> | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [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) are involved in many biological processes such as fibrinolysis or inflammation, development, Alzheimer's disease, and various types of cancer. We describe the synthesis and kinetic characterization of a focused library of 22 thiirane- and oxirane-based potential mechanism-based inhibitors, which led to discovery of an inhibitor for the human pro-carboxypeptidase A1. Our structural analyses show that the thiirane-based small-molecule inhibitor penetrates the barrier of the pro-domain to bind within the active site. This binding leads to a chemical reaction that covalently modifies the catalytic Glu270. These results highlight the importance of combined structural, biophysical, and biochemical evaluation of inhibitors in design strategies for the development of spectroscopically nonsilent probes as effective beacons for in vitro, in cellulo, and/or in vivo localization in clinical and industrial applications. | ||
| + | |||
| + | Discovery of Mechanism-Based Inactivators for Human Pancreatic Carboxypeptidase A from a Focused Synthetic Library.,Testero SA, Granados C, Fernandez D, Gallego P, Covaleda G, Reverter D, Vendrell J, Aviles FX, Pallares I, Mobashery S ACS Med Chem Lett. 2017 Sep 22;8(10):1122-1127. doi:, 10.1021/acsmedchemlett.7b00346. eCollection 2017 Oct 12. PMID:29057062<ref>PMID:29057062</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5om9" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: Aviles | + | [[Category: Large Structures]] |
| - | [[Category: Covaleda | + | [[Category: Aviles FX]] |
| - | [[Category: Fernandez | + | [[Category: Covaleda G]] |
| - | [[Category: Gallego | + | [[Category: Fernandez D]] |
| - | [[Category: Granados | + | [[Category: Gallego P]] |
| - | [[Category: Pallares | + | [[Category: Granados C]] |
| - | [[Category: Reverter | + | [[Category: Pallares I]] |
| - | [[Category: Vendrell | + | [[Category: Reverter D]] |
| - | + | [[Category: Vendrell J]] | |
Current revision
Crystal structure of the human CARBOXYPEPTIDASE A1 in complex with a thiirane mechanism-based inhibitor
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