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6gid

From Proteopedia

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High resolution crystal structure of substrate-free human neprilysin

Structural highlights

6gid 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:	, , , , , ,
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 is a transmembrane M13 zinc metalloprotease responsible for the degradation of several biologically active peptides including insulin, enkephalin, substance P, bradykinin, endothelin-1, neurotensin and amyloid-beta. The protein has received attention for its role in modulating blood pressure responses with its inhibition producing an antihypertensive response. To date, several inhibitor bound crystal structures of the human neprilysin extracellular domain have been determined, but, a structure free of bound inhibitor or substrate has yet to be reported. Here, we report the first crystal structure free of substrate or inhibitor for the extracellular catalytic domain of human neprilysin at 1.9A resolution. This structure will provide a reference point for comparisons to future inhibitor or substrate bound structures. The neprilysin structure also reveals that a closed protein conformation can be adopted in protein crystals absent of bound substrate or inhibitor.

High resolution crystal structure of substrate-free human neprilysin.,Moss S, Subramanian V, Acharya KR J Struct Biol. 2018 Jun 12. pii: S1047-8477(18)30142-4. doi:, 10.1016/j.jsb.2018.06.004. PMID:29906506^[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
↑ Moss S, Subramanian V, Acharya KR. High resolution crystal structure of substrate-free human neprilysin. J Struct Biol. 2018 Jun 12. pii: S1047-8477(18)30142-4. doi:, 10.1016/j.jsb.2018.06.004. PMID:29906506 doi:http://dx.doi.org/10.1016/j.jsb.2018.06.004

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 3: / Line 3: @@
 <StructureSection load='6gid' size='340' side='right' caption='[[6gid]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6gid]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GID OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GID FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6gid]] 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=6GID OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GID FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=6gid FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gid OCA], [http://pdbe.org/6gid PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gid RCSB], [http://www.ebi.ac.uk/pdbsum/6gid PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gid ProSAT]</span></td></tr>
@@ Line 19: / Line 20: @@
 </div>
 <div class="pdbe-citations 6gid" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Neprilysin|Neprilysin]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Neprilysin]]
 [[Category: Acharya, K R]]

6gid

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Current revision

High resolution crystal structure of substrate-free human neprilysin

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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