1DMT

STRUCTURE OF HUMAN NEUTRAL ENDOPEPTIDASE COMPLEXED WITH PHOSPHORAMIDON

1DMT の概要

• エントリーDOI: 10.2210/pdb1dmt/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000638
• 分子名称: NEUTRAL ENDOPEPTIDASE, 2-acetamido-2-deoxy-beta-D-glucopyranose, ZINC ION, ... (6 entities in total)
• 機能のキーワード: hydrolase, metalloprotease, signal-anchor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane; Single-pass type II membrane protein: P08473
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 80890.14

構造登録者

Oefner, C.,D'Arcy, A.,Hennig, M.,Winkler, F.K.,Dale, G.E. (登録日: 1999-12-15, 公開日: 2000-12-20, 最終更新日: 2024-11-13)

主引用文献

Oefner, C.,D'Arcy, A.,Hennig, M.,Winkler, F.K.,Dale, G.E.
Structure of human neutral endopeptidase (Neprilysin) complexed with phosphoramidon.
J.Mol.Biol., 296:341-349, 2000

PubMed Abstract: Neutral endopeptidase is a mammalian type II integral membrane zinc-containing endopeptidase, which degrades and inactivates a number of bioactive peptides. The range of substrates cleaved by neutral endopeptidase in vitro includes the enkephalins, substance P, endothelin, bradykinin and atrial natriuretic factor. Due to the physiological importance of neutral endopeptidase in the modulation of nociceptive and pressor responses there is considerable interest in inhibitors of this enzyme as novel analgesics and anti-hypertensive agents. Here we describe the crystal structure of the extracellular domain (residues 52-749) of human NEP complexed with the generic metalloproteinase inhibitor phosphoramidon at 2.1 A resolution. The structure reveals two multiply connected folding domains which embrace a large central cavity containing the active site. The inhibitor is bound to one side of this cavity and its binding mode provides a detailed understanding of the ligand-binding and specificity determinants.

PubMed: 10669592
DOI: 10.1006/jmbi.1999.3492

実験手法

X-RAY DIFFRACTION (2.1 Å)