View source for 8vjy


==Structure of Human Neurolysin in complex with Neurotensin peptide==
<StructureSection load='8vjy' size='340' side='right'caption='[[8vjy]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8vjy]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8VJY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8VJY 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]] 1.95&#8491;</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=8vjy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8vjy OCA], [https://pdbe.org/8vjy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8vjy RCSB], [https://www.ebi.ac.uk/pdbsum/8vjy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8vjy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NEUL_HUMAN NEUL_HUMAN] Hydrolyzes oligopeptides such as neurotensin, bradykinin and dynorphin A.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A zinc metallopeptidase neurolysin (Nln) processes diverse bioactive peptides to regulate signaling in the mammalian nervous system. To understand how Nln interacts with various peptides with dissimilar sequences, we determined crystal structures of Nln in complex with diverse peptides including dynorphins, angiotensin, neurotensin, and bradykinin. The structures show that Nln binds these peptides in a large dumbbell-shaped interior cavity constricted at the active site, making minimal structural changes to accommodate different peptide sequences. The structures also show that Nln readily binds similar peptides with distinct registers, which can determine whether the peptide serves as a substrate or a competitive inhibitor. We analyzed the activities and binding of Nln toward various forms of dynorphin A peptides, which highlights the promiscuous nature of peptide binding and shows how dynorphin A (1-13) potently inhibits the Nln activity while dynorphin A (1-8) is efficiently cleaved. Our work provides insights into the broad substrate specificity of Nln and may aid in the future design of small molecule modulators for Nln.

Structural basis of divergent substrate recognition and inhibition of human neurolysin.,Shi K, Bagchi S, Bickel J, Esfahani SH, Yin L, Cheng T, Karamyan VT, Aihara H Sci Rep. 2024 Aug 8;14(1):18420. doi: 10.1038/s41598-024-67639-w. PMID:39117724<ref>PMID:39117724</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8vjy" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Aihara H]]
[[Category: Shi K]]