High resolution crystal structure of substrate-free human neprilysin

Research output: Contribution to journalArticle

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Abstract

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-β. 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 1.9 Å 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.

Original languageEnglish
Pages (from-to)19-25
Number of pages7
JournalJournal of Structural Biology
Volume204
Issue number1
Early online date12 Jun 2018
DOIs
Publication statusPublished - 1 Oct 2018

Fingerprint

Neprilysin
Neurotensin
Protein Conformation
Enkephalins
Metalloproteases
Bradykinin
Endothelin-1
Substance P
Amyloid
Antihypertensive Agents
Zinc
Catalytic Domain
Proteins
Insulin
Blood Pressure
Peptides

Keywords

  • Crystallography
  • Neprilysin
  • Protein structure
  • Substrate-free
  • Zinc metalloprotease

ASJC Scopus subject areas

  • Structural Biology

Cite this

High resolution crystal structure of substrate-free human neprilysin. / Moss, Stephen; Subramanian, Vasanta; Acharya, K Ravi.

In: Journal of Structural Biology, Vol. 204, No. 1, 01.10.2018, p. 19-25.

Research output: Contribution to journalArticle

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