A New Class of EutT ATP:Co(I)rrinoid Adenosyltransferases Found in Listeria monocytogenes and Other Firmicutes Does Not Require a Metal Ion for Activity

Biochemistry. 2018 Aug 28;57(34):5076-5087. doi: 10.1021/acs.biochem.8b00715. Epub 2018 Aug 16.

Abstract

ATP:Co(I)rrinoid adenosyltransferases (ACATs) are involved in de novo adenosylcobamide (AdoCba) biosynthesis and in salvaging complete and incomplete corrinoids from the environment. The ACAT enzyme family is comprised of three classes of structurally and evolutionarily distinct proteins (i.e., CobA, PduO, and EutT). The structure of EutT is unknown, and an understanding of its mechanism is incomplete. The Salmonella enterica EutT ( SeEutT) enzyme is the best-characterized member of its class and is known to be a ferroprotein. Here, we report the identification and initial biochemical characterization of an enzyme representative of a new class of EutTs that does not require a metal ion for activity. In vivo and in vitro evidence shows that the metal-free EutT homologue from Listeria monocytogenes ( LmEutT) has ACAT activity and that, unlike other ACATs, the biologically active form of LmEutT is a tetramer. In vitro studies revealed that LmEutT was more efficient than SeEutT and displayed positive cooperativity. LmEutT adenosylated cobalamin, but not cobinamide, showed specificity for ATP and 2'-deoxyATP and released a triphosphate byproduct. Bioinformatics analyses suggest that metal-free EutT ACATs are also present in other Firmicutes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Alkyl and Aryl Transferases / chemistry
  • Alkyl and Aryl Transferases / metabolism*
  • Amino Acid Sequence
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Cobamides / metabolism*
  • Computational Biology
  • Firmicutes / enzymology*
  • Kinetics
  • Listeria monocytogenes / enzymology*
  • Metals / metabolism*
  • Models, Molecular
  • Phylogeny
  • Protein Conformation
  • Sequence Homology

Substances

  • Bacterial Proteins
  • Cobamides
  • Metals
  • cobinamide
  • Adenosine Triphosphate
  • Alkyl and Aryl Transferases
  • ATP-corrinoid adenosyltransferase