1R1H

STRUCTURAL ANALYSIS OF NEPRILYSIN WITH VARIOUS SPECIFIC AND POTENT INHIBITORS

Summary for 1R1H

• Entry DOI: 10.2210/pdb1r1h/pdb
• Related: 1DMT 1R1I 1R1J
• Descriptor: Neprilysin, 2-acetamido-2-deoxy-beta-D-glucopyranose, ZINC ION, ... (5 entities in total)
• Functional Keywords: enkephalinase, glycoprotein, metalloprotease, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Single-pass type II membrane protein: P08473
• Total number of polymer chains: 1
• Total formula weight: 80672.96

Authors

Oefner, C.,Roques, B.P.,Fournie-Zaluski, M.C.,Dale, G.E. (deposition date: 2003-09-24, release date: 2004-09-28, Last modification date: 2020-07-29)

Primary citation

Oefner, C.,Roques, B.P.,Fournie-Zaluski, M.C.,Dale, G.E.
Structural analysis of neprilysin with various specific and potent inhibitors.
Acta Crystallogr.,Sect.D, 60:392-396, 2004

PubMed Abstract: Neutral endopeptidase (NEP) is the major enzyme involved in the metabolic inactivation of a number of bioactive peptides including the enkephalins, substance P, endothelin, bradykinin and atrial natriuretic factor. Owing to the physiological importance of NEP in the modulation of nociceptive and pressor responses, there is considerable interest in inhibitors of this enzyme as novel analgesics and antihypertensive agents. Here, the crystal structures of the soluble extracellular domain of human NEP (residues 52-749) complexed with various potent and competitive inhibitors are described. The structures unambiguously reveal the binding mode of the different zinc-chelating groups and the subsite specificity of the enzyme.

PubMed: 14747736
DOI: 10.1107/S0907444903027410

Experimental method

X-RAY DIFFRACTION (1.95 Å)