8vjv

Structure of Human Neurolysin in complex with dynorphin A8(1-8) peptide

spinqualitylabelsall models 8vjv, resolution 2.12Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8vjv is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.12Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NEUL_HUMAN Hydrolyzes oligopeptides such as neurotensin, bradykinin and dynorphin A. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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