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

Abstract Human 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 no...

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Bibliographic Details
Published in:Journal of biochemistry (Tokyo) 2020-10, Vol.168 (4), p.417-425
Main Authors: Liu, Fan, Zhang, Jianyu
Format: Article
Language:English
Subjects:
Catalytic Domain
Catechol O-Methyltransferase - chemistry
Catechol O-Methyltransferase - genetics
Catechol O-Methyltransferase - metabolism
Catechols - metabolism
Fluorescence
Humans
Mutagenesis, Site-Directed - methods
Mutation
Recombinant Proteins - genetics
Recombinant Proteins - isolation & purification
Recombinant Proteins - metabolism
S-Adenosylmethionine - metabolism
Structure-Activity Relationship
Tryptophan - chemistry
Tryptophan - genetics
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Summary:Abstract Human 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.
ISSN:0021-924X
1756-2651
DOI:10.1093/jb/mvaa063