A point mutation converts dihydroneopterin aldolase to a cofactor-independent oxygenase |
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Authors: | Wang Yi Scherperel Gwynyth Roberts Kade D Jones A Daniel Reid Gavin E Yan Honggao |
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Affiliation: | Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, 48824, USA. |
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Abstract: | 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. |
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