Article
Potentiating AZT activation: structures of wild-type and mutant human thymidylate kinase suggest reasons for the mutants' improved kinetics with the HIV prodrug metabolite AZTMP.
Journal of molecular biology - 17 Nov 2000
Ostermann N, Lavie A, Padiyar S, Brundiers R, Veit T, Reinstein J, Goody R S, Konrad M, Schlichting I
Abstract excerpt
The 60-fold reduced phosphorylation rate of azidothymidine (AZT) monophosphate (AZTMP), the partially activated AZT metabolite, by human thymidylate kinase (TMPK) severely limits the efficacy of this anti-HIV prodrug. Crystal structures of different TMPK nucleotide complexes indicate that steric hindrance by the azido group of AZTMP prevents formation of the catalytically active closed conformation of the P-loop...
Read the complete abstract on PubMedTopics
Share this publication in a Topic to start or enrich a Post.