View source for 8vju


==Structure of Human Neurolysin in complex with dynorphin A13 peptide==
<StructureSection load='8vju' size='340' side='right'caption='[[8vju]], [[Resolution|resolution]] 1.99&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8vju]] is a 2 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=8VJU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8VJU 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]] 1.99&#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=8vju FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8vju OCA], [https://pdbe.org/8vju PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8vju RCSB], [https://www.ebi.ac.uk/pdbsum/8vju PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8vju ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NEUL_HUMAN NEUL_HUMAN] Hydrolyzes oligopeptides such as neurotensin, bradykinin and dynorphin A.
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== 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>
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== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Aihara H]]
[[Category: Shi K]]