Exploiting glycogen synthase kinase 3beta flexibility in molecular recognition.
GSK3beta (glycogen synthase kinase 3beta) is involved in the phosphorylation of various important regulatory proteins. Pharmacological inhibition of this enzyme could yield treatments for a variety of diseases including diabetes and Alzheimer's disease. The understanding of events involved in the molecular recognition of inhibitors by the active site of this enzyme is key in structure-based design strategies. The present study deals with the dynamic nature of GSK3beta and highlights the importance of studying protein plasticity in structure-based drug design, exemplified by our method called ASP (active-site pressurization).
Mazanetz
Michael P
MP
Centre for Biomolecular Sciences and School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, U.K.
Withers
Ian M
IM
Laughton
Charles A
CA
Fischer
Peter M
PM
D003198:Computer Simulation; D038362:Glycogen Synthase Kinase 3 / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D008958:Models, Molecular; D018583:Pliability; D021281:Quantitative Structure-Activity Relationship
D008024:Ligands; D038362:Glycogen Synthase Kinase 3