2qpj
From Proteopedia
(New page: 200px<br /><applet load="2qpj" size="350" color="white" frame="true" align="right" spinBox="true" caption="2qpj, resolution 2.05Å" /> '''Human NEP complexed ...) |
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==Overview== | ==Overview== | ||
| - | Neutral endopeptidase (NEP) is the major enzyme involved in the metabolic | + | 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== | ==About this Structure== | ||
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[[Category: Neprilysin]] | [[Category: Neprilysin]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Dale, G | + | [[Category: Dale, G E.]] |
[[Category: Oefner, C.]] | [[Category: Oefner, C.]] | ||
[[Category: I20]] | [[Category: I20]] | ||
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[[Category: zinc-dependent metalloprotease]] | [[Category: zinc-dependent metalloprotease]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:41:10 2008'' |
Revision as of 16:41, 21 February 2008
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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 , and 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
Page seeded by OCA on Thu Feb 21 18:41:10 2008
Categories: Homo sapiens | Neprilysin | Single protein | Dale, G E. | Oefner, C. | I20 | NAG | ZN | Glycoprotein | Hydrolase | Lt3 9 | Membrane | Metal-binding | Signal-anchor | Transmembrane | Zinc-dependent metalloprotease
