Role of a critical water in scytalone dehydratase-catalyzed reaction

被引:16
作者
Zheng, YJ [1 ]
Bruice, TC [1 ]
机构
[1] Univ Calif Santa Barbara, Dept Chem, Santa Barbara, CA 93106 USA
关键词
D O I
10.1073/pnas.95.8.4158
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Scytalone dehydratase (EC 4.2.1.94) catalyzes the dehydration of two important intermediates in the biosynthesis of melanin, and it functions without metal ions or any cofactors, Using molecular orbital theory, we have examined the role of a critical water molecule in the mechanism of scytalone dehydratase. The water, together with an internal hydrogen bonding, contributes significantly to the stabilization of the transition state (or the enolate intermediate). The role of two active site tyrosines (Tpr-50 and Tyr-30) is (i) to hold the critical water in place so that it may stabilize the transition state without much structural rearrangement during the catalytic reaction, and (ii) to polarize the water, making it a better general acid. The stereochemistry of the scytalone dehydratase-catalyzed dehydration is also discussed.
引用
收藏
页码:4158 / 4163
页数:6
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