6xvp
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6xvp is ON HOLD until Paper Publication Authors: Cozier, G.E., Acharya, K.R., Sharma, U. Description: Crystal structure of Neprilysin in complex wi...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of Neprilysin in complex with Sampatrilat.== | |
| + | <StructureSection load='6xvp' size='340' side='right'caption='[[6xvp]], [[Resolution|resolution]] 2.65Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XVP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XVP 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]] 2.65Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D0Z:Sampatrilat'>D0Z</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=6xvp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xvp OCA], [https://pdbe.org/6xvp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xvp RCSB], [https://www.ebi.ac.uk/pdbsum/6xvp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xvp ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Neprilysin (NEP) and angiotensin-converting enzyme (ACE) are two key zinc-dependent metallopeptidases in the natriuretic peptide and kinin systems and renin-angiotensin-aldosterone system, respectively. They play an important role in blood pressure regulation and reducing the risk of heart failure. Vasopeptidase inhibitors omapatrilat and sampatrilat possess dual activity against these enzymes by blocking the ACE-dependent conversion of angiotensin I to the potent vasoconstrictor angiotensin II while simultaneously halting the NEP-dependent degradation of vasodilator atrial natriuretic peptide. Here, we report crystal structures of omapatrilat, sampatrilat, and sampatrilat-ASP (a sampatrilat analogue) in complex with NEP at 1.75, 2.65, and 2.6 A, respectively. A detailed analysis of these structures and the corresponding structures of ACE with these inhibitors has provided the molecular basis of dual inhibitor recognition involving the catalytic site in both enzymes. This new information will be very useful in the design of safer and more selective vasopeptidase inhibitors of NEP and ACE for effective treatment in hypertension and heart failure. | ||
| - | + | Molecular Basis for Omapatrilat and Sampatrilat Binding to Neprilysin-Implications for Dual Inhibitor Design with Angiotensin-Converting Enzyme.,Sharma U, Cozier GE, Sturrock ED, Acharya KR J Med Chem. 2020 May 8. doi: 10.1021/acs.jmedchem.0c00441. PMID:32337993<ref>PMID:32337993</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Acharya | + | <div class="pdbe-citations 6xvp" style="background-color:#fffaf0;"></div> |
| - | [[Category: Cozier | + | |
| - | [[Category: Sharma | + | ==See Also== |
| + | *[[Neprilysin|Neprilysin]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Acharya KR]] | ||
| + | [[Category: Cozier GE]] | ||
| + | [[Category: Sharma U]] | ||
Current revision
Crystal structure of Neprilysin in complex with Sampatrilat.
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