1r1j: Difference between revisions

Revision as of 13:16, 16 December 2020

STRUCTURAL ANALYSIS OF NEPRILYSIN WITH VARIOUS SPECIFIC AND POTENT INHIBITORS

Structural highlights

1r1j 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:	NAG, OIR, ZN
Related:	1dmt, 1r1h, 1r1i
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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Neutral endopeptidase (NEP) is the major enzyme involved in the metabolic inactivation of a number of bioactive peptides including the enkephalins, substance P, endothelin, bradykinin and atrial natriuretic factor. Owing to the physiological importance of NEP in the modulation of nociceptive and pressor responses, there is considerable interest in inhibitors of this enzyme as novel analgesics and antihypertensive agents. Here, the crystal structures of the soluble extracellular domain of human NEP (residues 52-749) complexed with various potent and competitive inhibitors are described. The structures unambiguously reveal the binding mode of the different zinc-chelating groups and the subsite specificity of the enzyme.

Structural analysis of neprilysin with various specific and potent inhibitors.,Oefner C, Roques BP, Fournie-Zaluski MC, Dale GE Acta Crystallogr D Biol Crystallogr. 2004 Feb;60(Pt 2):392-6. Epub 2004, Jan 23. PMID:14747736^[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:https://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:https://dx.doi.org/10.1074/jbc.M110.161547
↑ Oefner C, Roques BP, Fournie-Zaluski MC, Dale GE. Structural analysis of neprilysin with various specific and potent inhibitors. Acta Crystallogr D Biol Crystallogr. 2004 Feb;60(Pt 2):392-6. Epub 2004, Jan 23. PMID:14747736 doi:10.1107/S0907444903027410

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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:https://dx.doi.org/10.1042/BJ20040634

[3] 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:https://dx.doi.org/10.1074/jbc.M110.161547

[4] Oefner C, Roques BP, Fournie-Zaluski MC, Dale GE. Structural analysis of neprilysin with various specific and potent inhibitors. Acta Crystallogr D Biol Crystallogr. 2004 Feb;60(Pt 2):392-6. Epub 2004, Jan 23. PMID:14747736 doi:10.1107/S0907444903027410

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[2]

[3]

[4]

@@ Line 1: / Line 1: @@
 ==STRUCTURAL ANALYSIS OF NEPRILYSIN WITH VARIOUS SPECIFIC AND POTENT INHIBITORS==
-<StructureSection load='1r1j' size='340' side='right' caption='[[1r1j]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
+<StructureSection load='1r1j' size='340' side='right'caption='[[1r1j]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1r1j]] 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=1R1J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1R1J FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1r1j]] 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=1R1J OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1R1J FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=OIR:N-(3-PHENYL-2-SULFANYLPROPANOYL)PHENYLALANYLALANINE'>OIR</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=OIR:N-(3-PHENYL-2-SULFANYLPROPANOYL)PHENYLALANYLALANINE'>OIR</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">[[1dmt|1dmt]], [[1r1h|1r1h]], [[1r1i|1r1i]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1dmt|1dmt]], [[1r1h|1r1h]], [[1r1i|1r1i]]</div></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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1r1j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r1j OCA], [http://pdbe.org/1r1j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1r1j RCSB], [http://www.ebi.ac.uk/pdbsum/1r1j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1r1j ProSAT]</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=1r1j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r1j OCA], [http://pdbe.org/1r1j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1r1j RCSB], [http://www.ebi.ac.uk/pdbsum/1r1j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1r1j ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 39: / Line 39: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Neprilysin]]
 [[Category: Dale, G E]]

1r1j: Difference between revisions

Revision as of 13:16, 16 December 2020

STRUCTURAL ANALYSIS OF NEPRILYSIN WITH VARIOUS SPECIFIC AND POTENT INHIBITORS

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

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