Nano-second protein dynamics of key residue at Position 38 in catechol-O-methyltransferase system: a time-resolved fluorescence study

Abstract

AbstractHuman catechol-O-methyltransferase, a key enzyme related to neurotransmitter metabolism, catalyses a methyl transfer from S-adenosylmethionine to catechol. Although extensive studies aim to understand the enzyme mechanisms, the connection of protein dynamics and enzyme catalysis is still not clear. Here, W38in (Trp143Phe) and W38in/Y68A (Trp143Phe with Tyr68Ala) mutants were carried out to study the relationship of dynamics and catalysis in nano-second timescale using time-resolved fluorescence lifetimes and Stokes shifts in various solvents. The comprehensive data implied the mutant W38in/Y68A with lower activity is more rigid than the ‘WT’−W38in, suggesting the importance of flexibility at residue 38 to maintain the optimal catalysis.