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6suk

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Revision as of 06:41, 10 June 2020

Crystal structure of Neprilysin in complex with Omapatrilat.

Structural highlights

6suk is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Related:	6gid
Gene:	MME, EPN (HUMAN)
Activity:	Neprilysin, with EC number 3.4.24.11
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[NEP_HUMAN] Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids. Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond. Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9. Involved in the degradation of atrial natriuretic factor (ANF). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers.^[1] ^[2] ^[3]

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yandle TG, Brennan SO, Espiner EA, Nicholls MG, Richards AM. Endopeptidase-24.11 in human plasma degrades atrial natriuretic factor (ANF) to ANF(99-105/106-126). Peptides. 1989 Jul-Aug;10(4):891-4. PMID:2531377
↑ Rice GI, Thomas DA, Grant PJ, Turner AJ, Hooper NM. Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism. Biochem J. 2004 Oct 1;383(Pt 1):45-51. PMID:15283675 doi:http://dx.doi.org/10.1042/BJ20040634
↑ Morisaki N, Moriwaki S, Sugiyama-Nakagiri Y, Haketa K, Takema Y, Imokawa G. Neprilysin is identical to skin fibroblast elastase: its role in skin aging and UV responses. J Biol Chem. 2010 Dec 17;285(51):39819-27. doi: 10.1074/jbc.M110.161547. Epub, 2010 Sep 28. PMID:20876573 doi:http://dx.doi.org/10.1074/jbc.M110.161547
↑ Sharma U, Cozier GE, Sturrock ED, Acharya KR. Molecular Basis for Omapatrilat and Sampatrilat Binding to Neprilysin-Implications for Dual Inhibitor Design with Angiotensin-Converting Enzyme. J Med Chem. 2020 May 8. doi: 10.1021/acs.jmedchem.0c00441. PMID:32337993 doi:http://dx.doi.org/10.1021/acs.jmedchem.0c00441

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6suk"

@@ Line 3: / Line 3: @@
 <StructureSection load='6suk' size='340' side='right'caption='[[6suk]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6suk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SUK OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6SUK FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6suk]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SUK OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6SUK FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FT8:Omapatrilat'>FT8</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6gid|6gid]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MME, EPN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Neprilysin Neprilysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.11 3.4.24.11] </span></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6suk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6suk OCA], [http://pdbe.org/6suk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6suk RCSB], [http://www.ebi.ac.uk/pdbsum/6suk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6suk ProSAT]</span></td></tr>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Neprilysin]]

6suk

From Proteopedia

Revision as of 06:41, 10 June 2020

Crystal structure of Neprilysin in complex with Omapatrilat.

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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