2fb2
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Structure of the MoaA Arg17/266/268/Ala triple mutant
OverviewOverview
The first step in molybdenum cofactor biosynthesis, the conversion of, 5'-GTP to precursor Z, an oxygen-sensitive tetrahydropyranopterin is, catalyzed by the S-adenosylmethionine (SAM)-dependent enzyme MoaA and the, accessory protein MoaC. This reaction involves the radical-initiated, intramolecular rearrangement of the guanine C8 atom. MoaA harbors an, N-terminal [4Fe-4S] cluster, which is involved in the reductive cleavage, of SAM and generates a 5'-deoxyadenosyl radical (5'-dA*), and a C-terminal, [4Fe-4S] cluster presumably involved in substrate binding and/or, activation. Biochemical studies identified residues involved in 5'-GTP, binding and the determinants of nucleotide specificity. The crystal, structure of MoaA in complex with 5'-GTP confirms the biochemical data and, provides valuable insights into the subsequent radical reaction. MoaA, binds 5'-GTP with high affinity and interacts through its C-terminal, [4Fe-4S] cluster with the guanine N1 and N2 atoms, in a yet, uncharacterized binding mode. The tightly anchored triphosphate moiety, prevents the escape of radical intermediates. This structure also, visualizes the L-Met and 5'-dA cleavage products of SAM. Rotation of the, 5'-dA ribose and/or conformational changes of the guanosine are proposed, to bring the 5'-deoxyadenosyl radical into close proximity of either the, ribose C2' and C3' or the guanine C8 carbon atoms leading to hydrogen, abstraction.
About this StructureAbout this Structure
2FB2 is a Single protein structure of sequence from Staphylococcus aureus with SO4, SAM and SF4 as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Binding of 5'-GTP to the C-terminal FeS cluster of the radical S-adenosylmethionine enzyme MoaA provides insights into its mechanism., Hanzelmann P, Schindelin H, Proc Natl Acad Sci U S A. 2006 May 2;103(18):6829-34. Epub 2006 Apr 21. PMID:16632608 [[Category: [4fe-4s] clusters]]
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