Equatorial Active Site Compaction and Electrostatic Reorganization in Catechol-<i>O</i>-methyltransferase.

ABSTRACT: Catechol-O-methyltransferase (COMT) is a model S-adenosyl-l-methionine (SAM) dependent methyl transferase, which catalyzes the methylation of catecholamine neurotransmitters such as dopamine in the primary pathway of neurotransmitter deactivation in animals. Despite extensive study, there is no consensus view of the physical basis of catalysis in COMT. Further progress requires experimental data that directly probes active site geometry, protein dynamics and electrostatics, ideally in a range of positions along the reaction coordinate. Here we establish that sinefungin, a fungal-derived inhibitor of SAM-dependent enzymes that possess transition state-like charge on the transferring group, can be used as a transition state analog of COMT when combined with a catechol. X-ray crystal s

SUBMITTER: Czarnota S 

PROVIDER: S-EPMC6503465 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature