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Molybdopterin biosynthesis: trapping of intermediates for the MoaA-catalyzed reaction using 2'-deoxyGTP and 2'-chloroGTP as substrate analogues.

ABSTRACT: MoaA is a radical S-adenosylmethionine (AdoMet) enzyme that catalyzes a complex rearrangement of guanosine-5'-triphosphate (GTP) in the first step of molybdopterin biosynthesis. In this paper, we provide additional characterization of the MoaA reaction product, describe the use of 2'-chloroGTP to trap the GTP C3' radical, generated by hydrogen atom transfer to the 5'-deoxyadenosyl radical, and the use of 2'-deoxyGTP to block a late step in the reaction sequence. These probes, coupled with the previously reported trapping of an intermediate in which C3' of the ribose is linked to C8 of the purine, allow us to propose a plausible mechanism for the MoaA-catalyzed reaction.

SUBMITTER: Mehta AP

PROVIDER: S-EPMC4227724 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Molybdopterin biosynthesis: trapping of intermediates for the MoaA-catalyzed reaction using 2'-deoxyGTP and 2'-chloroGTP as substrate analogues.

Mehta Angad P AP Abdelwahed Sameh H SH Xu Hui H Begley Tadhg P TP

Journal of the American Chemical Society 20140718 30

MoaA is a radical S-adenosylmethionine (AdoMet) enzyme that catalyzes a complex rearrangement of guanosine-5'-triphosphate (GTP) in the first step of molybdopterin biosynthesis. In this paper, we provide additional characterization of the MoaA reaction product, describe the use of 2'-chloroGTP to trap the GTP C3' radical, generated by hydrogen atom transfer to the 5'-deoxyadenosyl radical, and the use of 2'-deoxyGTP to block a late step in the reaction sequence. These probes, coupled with the pr ...[more]

PMID: 24955657

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