Abstract
A series of non-covalent inhibitors of the serine protease dipeptidyl peptidase IV (DPP-IV) were found to adopt a U-shaped binding conformation in X-ray co-crystallization studies. Remarkably, Tyr547 undergoes a 70 degrees side-chain rotation to accommodate the inhibitor and allows access to a previously unexposed area of the protein backbone for hydrogen bonding.
MeSH terms
-
Animals
-
Binding Sites
-
Computer Simulation
-
Crystallography, X-Ray
-
Dipeptidyl Peptidase 4 / blood
-
Dipeptidyl-Peptidase IV Inhibitors*
-
Drug Evaluation, Preclinical
-
Hydrogen Bonding
-
Male
-
Models, Molecular
-
Molecular Conformation
-
Protease Inhibitors / chemical synthesis*
-
Protease Inhibitors / chemistry
-
Protease Inhibitors / pharmacology*
-
Rats
-
Rats, Wistar
-
Spectrometry, Fluorescence
Substances
-
Dipeptidyl-Peptidase IV Inhibitors
-
Protease Inhibitors
-
Dipeptidyl Peptidase 4