Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:6.2.1.1 (
ACS
)
78,556
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The conformational profiles for the endogenous peptide
Opiorphin
and a set of seven analogues exhibiting different inhibitory activities toward human aminopeptidase N (hAPN) and human neprilysin (hNEP) were independently computed to deduce a bioactive conformation that
Opiorphin
may adopt when binding these two enzymes. The conformational space was thoroughly sampled using an iterative simulated annealing protocol, and a library of low-energy conformers was generated for each peptide. Bioactive
Opiorphin
conformations fitting our experimental structure-activity relationship data were identified for hAPN and hNEP using computational pairwise comparisons between each of the unique low-energy conformations of
Opiorphin
and its analogues. The obtained results provide a structural explanation for the dual hAPN and hNEP inhibitory activity of
Opiorphin
and show that the inborn flexibility of
Opiorphin
is essential for its analgesic activity.
ACS
Med Chem Lett 2012 Jan 12
PMID:Proposed Bioactive Conformations of Opiorphin, an Endogenous Dual APN/NEP Inhibitor. 2490 Mar 67
