2qpj | pdb_00002qpj
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Human NEP complexed with a bifunctional NEP/DPP IV inhibitor
Overview
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, as well, as the incretin hormone glucagon-like peptide 1 (GLP-1), which is a potent, stimulator of insulin secretion. The activity of GLP-1 is also rapidly, abolished by the serine protease dipeptidyl peptidase IV (DPP-IV), which, led to an elevated interest in inhibitors of this enzyme for the treatment, of type II diabetes. A dual NEP/DPP-IV inhibitor concept is proposed, offering an alternative strategy for the treatment of type 2 diabetes., Here, the synthesis and crystal structures of the soluble extracellular, domain of human NEP (residues 52-749) complexed with the NEP, competitive, and potent dual NEP/DPP-IV inhibitor MCB3937 are described.
About this Structure
2QPJ is a Single protein structure of sequence from Homo sapiens with NAG, ZN and I20 as ligands. Active as Neprilysin, with EC number 3.4.24.11 Full crystallographic information is available from OCA.
Reference
Structural studies of a bifunctional inhibitor of neprilysin and DPP-IV., Oefner C, Pierau S, Schulz H, Dale GE, Acta Crystallogr D Biol Crystallogr. 2007 Sep;63(Pt 9):975-81. Epub 2007, Aug 17. PMID:17704566
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