title: Product inhibition in the radical S-adenosylmethionine family.
abstract: Members of the radical S-adenosylmethionine (AdoMet) superfamily reductively cleave AdoMet to generate the highly reactive 5'-deoxyadenosyl radical (DOA()) which initiates biological transformations by abstraction of a hydrogen atom. We demonstrate that three members of the family: biotin synthase (BioB), lipoyl synthase (LipA) and tyrosine lyase (ThiH) are inhibited in vitro by a combination of the products 5'-deoxyadenosine (DOA) and methionine. These results suggest the observed inhibition is a common feature of the radical AdoMet proteins that form DOA and methionine as products. Addition of 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) to BioB, LipA or ThiH activity assays removed the product inhibition by catalysing the hydrolysis of DOA and gave an increase in activity.
authors.affiliation: School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Challand
authors.forename: Tillman
authors.initials: T
authors.lastname: Ziegert
authors.forename: Paul
authors.initials: P
authors.lastname: Douglas
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wood
authors.forename: Marco
authors.initials: M
authors.lastname: Kriek
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Shaw
authors.forename: Peter L
authors.initials: PL
authors.lastname: Roach