Phosphomethylpyrimidine synthase explained

Phosphomethylpyrimidine synthase
Ec Number:	4.1.99.17
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Phosphomethylpyrimidine synthase (thiC (gene)) is an enzyme with systematic name 5-amino-1-(5-phospho-D-ribosyl)imidazole formate-lyase (decarboxylating, 4-amino-2-methyl-5-phosphomethylpyrimidine-forming).^{[1] [2] [3]} This enzyme catalyses the following chemical reaction

\rightleftharpoons 4-amino-2-methyl-5-phosphomethylpyrimidine + 5′-deoxyadenosine + L-methionine + formate + CO

This enzyme binds a 4Fe-4S cluster.

The starting material is 5-aminoimidazole ribotide, which undergoes a rearrangement reaction via radical intermediates which incorporate the blue, green and red fragments shown into the product.^{[3] [4]}

Notes and References

1. Chatterjee A, Li Y, Zhang Y, Grove TL, Lee M, Krebs C, Booker SJ, Begley TP, Ealick SE . Reconstitution of ThiC in thiamine pyrimidine biosynthesis expands the radical SAM superfamily . Nature Chemical Biology . 4 . 12 . 758–65 . December 2008 . 18953358 . 2587053 . 10.1038/nchembio.121 .
2. Martinez-Gomez NC, Poyner RR, Mansoorabadi SO, Reed GH, Downs DM . Reaction of AdoMet with ThiC generates a backbone free radical . Biochemistry . 48 . 2 . 217–9 . January 2009 . 19113839 . 2654281 . 10.1021/bi802154j .
3. Chatterjee A, Hazra AB, Abdelwahed S, Hilmey DG, Begley TP . A "radical dance" in thiamin biosynthesis: mechanistic analysis of the bacterial hydroxymethylpyrimidine phosphate synthase . Angewandte Chemie . 49 . 46 . 8653–6 . November 2010 . 20886485 . 3147014 . 10.1002/anie.201003419 .
4. 10.1039/b207131m . Cofactor biosynthesis: An organic chemist's treasure trove . 2006 . Begley . Tadhg P. . Natural Product Reports . 23 . 1 . 15–18 . 16453030 .