6gid
From Proteopedia
High resolution crystal structure of substrate-free human neprilysin
Structural highlights
FunctionNEP_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 PubMedNeprilysin 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. See AlsoReferences
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