2QPJ

Human NEP complexed with a bifunctional NEP/DPP IV inhibitor

Summary for 2QPJ

• Entry DOI: 10.2210/pdb2qpj/pdb
• Descriptor: Neprilysin, 2-acetamido-2-deoxy-beta-D-glucopyranose, ZINC ION, ... (5 entities in total)
• Functional Keywords: zinc-dependent metalloprotease, glycoprotein, hydrolase, membrane, metal-binding, signal-anchor, transmembrane, lt3_9
• 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: 80804.10

Authors

Oefner, C.,Dale, G.E. (deposition date: 2007-07-24, release date: 2007-11-27, Last modification date: 2023-08-30)

Primary citation

Oefner, C.,Pierau, S.,Schulz, H.,Dale, G.E.
Structural studies of a bifunctional inhibitor of neprilysin and DPP-IV.
Acta Crystallogr.,Sect.D, 63:975-981, 2007

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, 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.

PubMed: 17704566
DOI: 10.1107/S0907444907036281

Experimental method

X-RAY DIFFRACTION (2.05 Å)