A Point Mutation Converts Dihydroneopterin Aldolase to a Cofactor-Independent Oxygenase
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- 作者：Yi Wang ; Gwynyth Scherperel ; Kade D. Roberts ; A. Daniel Jones ; Gavin E. Reid ; Honggao Yan
- 刊名：Journal of the American Chemical Society
- 出版年：2006
- 出版时间：October 11, 2006
- 年：2006
- 卷：128
- 期：40
- 页码：13216 - 13223
- 全文大小：157K
- 年卷期：v.128,no.40(October 11, 2006)
- ISSN：1520-5126
文摘
Dihydroneopterin aldolase (DHNA) catalyzes the conversion of 7,8-dihydroneopterin (1) to6-hydroxymethyl-7,8-dihydropterin (4) in the folate biosynthetic pathway. Substitution of a conserved tyrosineresidue at the active site of DHNA by phenylalanine converts the enzyme to a cofactor-independentoxygenase, which generates mainly 7,8-dihydroxanthopterin (6) rather than 4. 6 is generated via the sameenol intermediate as in the wild-type enzyme-catalyzed reaction, but this species undergoes an oxygenationreaction to form 6. The conserved tyrosine residue plays only a minor role in the formation of the enolreaction intermediate but a critical role in the protonation of the enol intermediate to form 4.