A point mutation converts dihydroneopterin aldolase to a cofactor-independent oxygenase

Yi Wang, Gwynyth Scherperel, Kade D. Roberts, A. Daniel Jones, Gavin E. Reid, Honggao Yan

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10 Citations (Scopus)


Dihydroneopterin aldolase (DHNA) catalyzes the conversion of 7,8-dihydroneopterin (1) to 6-hydroxymethyl-7,8-dihydropterin (4) in the folate biosynthetic pathway. Substitution of a conserved tyrosine residue at the active site of DHNA by phenylalanine converts the enzyme to a cofactor-independent oxygenase, which generates mainly 7,8-dihydroxanthopterin (6) rather than 4. 6 is generated via the same enol intermediate as in the wild-type enzyme-catalyzed reaction, but this species undergoes an oxygenation reaction to form 6. The conserved tyrosine residue plays only a minor role in the formation of the enol reaction intermediate but a critical role in the protonation of the enol intermediate to form 4.

Original languageEnglish
Pages (from-to)13216-13223
Number of pages8
JournalJournal of the American Chemical Society
Issue number40
Publication statusPublished - 11 Oct 2006
Externally publishedYes

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