2FB3

Structure of MoaA in complex with 5'-GTP

Summary for 2FB3

• Entry DOI: 10.2210/pdb2fb3/pdb
• Related: 1TV7 2FB2
• Descriptor: Molybdenum cofactor biosynthesis protein A, SULFATE ION, METHIONINE, ... (8 entities in total)
• Functional Keywords: s-adenosylmethionine, tim barrel, [4fe-4s] clusters, 5'-gtp, 5'-deoxyadenosine, ligand binding protein
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 2
• Total formula weight: 81109.15

Authors

Haenzelmann, P.,Schindelin, H. (deposition date: 2005-12-08, release date: 2006-05-09, Last modification date: 2024-02-14)

Primary citation

Haenzelmann, P.,Schindelin, H.
Binding of 5'-GTP to the C-terminal FeS cluster of the radical S-adenosylmethionine enzyme MoaA provides insights into its mechanism
Proc.Natl.Acad.Sci.USA, 103:6829-6834, 2006

PubMed Abstract: 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.

PubMed: 16632608
DOI: 10.1073/pnas.0510711103

Experimental method

X-RAY DIFFRACTION (2.349 Å)