PMID: 17704566

 

    Legend: Gene, Sites

Title : Structural studies of a bifunctional inhibitor of neprilysin and DPP-IV

Abstract :

1. 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
2. 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
3. A dual NEP / DPP-IV inhibitor concept is proposed, offering an alternative strategy for the treatment of type 2 diabetes
4. 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

Output (sent_index, trigger, protein, sugar, site):

Output(Part-Of) (sent_index, protein, site):

• 1. incretin hormone, peptide
• 4. NEP, domain

*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

Protein	NCBI ID	SENTENCE INDEX
substance P	6863	1
bradykinin	3827	1
Neutral endopeptidase	4311	1
DPP-IV	1803	0,2,3,4
neprilysin	4311	0
NEP	4311	1,3,4