9efo

Staphylococcus aureus MoaA C-terminal tail peptide in complex with G340A-MoaA

spinqualitylabelsall models 9efo Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9efo is a 1 chain structure with sequence from Staphylococcus aureus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, models Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MOAA_STAA1 Catalyzes the cyclization of GTP to (8S)-3',8-cyclo-7,8-dihydroguanosine 5'-triphosphate.[HAMAP-Rule:MF_01225] Publication Abstract from PubMed Metalloenzymes couple substrate binding and formation of oxidative intermediates to minimize unwanted side reactions. However, the molecular details of such coupling frequently remain ambiguous. Radical S-adenosyl-L-methionine (SAM) enzymes constitute one of the largest groups of metalloenzymes and catalyze various radical-mediated reactions. While radical SAM enzymes significantly accelerate the conserved radical initiation reaction, the reductive cleavage of SAM into 5'-deoxyadenosyl radical (5'-dA*), the molecular mechanism of this rate acceleration is largely unexplored. Here, using MoaA, aradical SAM enzyme in the molybdenum cofactor (Moco) biosynthesis, as a model, we reveal the mechanism of substrate-triggered radical initiation. We first elucidated the intact active site structure of MoaA using solution NMR characterization of the C-terminal tail, which was disordered in the reported crystal structures, and its computational docking into the MoaA structure. Together with the comprehensive functional validation, we show that MoaA uses its conformationally flexible C-terminal tail with two conserved Gly residues (GG motif) at the C-terminus as a sensor to detect substrate guanosine 5'-triphosphate (GTP) binding and trigger reductive SAM cleavage. Importantly, mutations that disrupt this regulatory mechanism cause Moco deficiency disease in humans. Comparison of these observations with other radical SAM enzymes provides insight into the general mechanism of substrate-triggered radical initiation in radical SAM enzymes. Mechanism of controlled radical initiation in radical SAM GTP 3',8-cyclase.,Pang H, Li D, Wu Q, Zhang P, Yang W, Silakov A, Zhou P, Yokoyama K Proc Natl Acad Sci U S A. 2025 Nov 11;122(45):e2502098122. doi: , 10.1073/pnas.2502098122. Epub 2025 Nov 3. PMID:41183211 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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