Structural basis of carnitine monooxygenase CntA substrate specificity, inhibition, and intersubunit electron transfer.

ABSTRACT: Microbial metabolism of carnitine to trimethylamine (TMA) in the gut can accelerate atherosclerosis and heart disease, and these TMA-producing enzymes are therefore important drug targets. Here, we report the first structures of the carnitine oxygenase CntA, an enzyme of the Rieske oxygenase family. CntA exists in a head-to-tail α₃ trimeric structure. The two functional domains (the Rieske and the catalytic mononuclear iron domains) are located >40 Å apart in the same monomer but adjacent in two neighboring monomers. Structural determination of CntA and subsequent electron paramagnetic resonance measurements uncover the molecular basis of the so-called bridging glutamate (E205) residue in intersubunit electron transfer. The structures of the substrate-bound CntA help to define t

SUBMITTER: Quareshy M 

PROVIDER: S-EPMC7948474 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature