Product inhibition in the radical S-adenosylmethionine family.
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.
Challand
Martin R
MR
School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK.
Ziegert
Tillman
T
Douglas
Paul
P
Wood
Robert J
RJ
Kriek
Marco
M
Shaw
Nicholas M
NM
Roach
Peter L
PL