Molecular dynamics derived life times of active substrate binding poses explain K _M of laccase mutants.

ABSTRACT: Fungal laccases (EC 1.10.3.2) are important multi-copper oxidases with broad substrate specificity. Laccases from Trametes versicolor (TvL) are among the best-characterized of these enzymes. Mutations in the substrate-binding site of TvL substantially affect K _M, but a molecular understanding of this effect is missing. We explored the effect of TvL mutations on K _M for the standard laccase substrate 2,6-dimethoxyphenol using 4500 ns of molecular dynamics, docking, and MMGBSA free energy computations. We show that changes in K _M due to mutation consistently correlate with the dynamics of the substrates within the substrate-binding site. We find that K _M depends on the lifetime ("dynamic stability") of the enzyme-

SUBMITTER: Mehra R 

PROVIDER: S-EPMC9089231 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature