Crystal Structure and Catalytic Mechanism of the MJ0109 Gene Product: A Bifunctional Enzyme with Inositol Monophosphatase and Fructose 1,6-Bisphosphatase Activities

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• 作者：Kenneth A. Johnson ; Liangjing Chen ; Hongying Yang ; Mary F. Roberts ; and Boguslaw Stec
• 刊名：Biochemistry
• 出版年：2001
• 出版时间：January 23, 2001
• 年：2001
• 卷：40
• 期：3
• 页码：618 - 630
• 全文大小：935K
• 年卷期：v.40,no.3(January 23, 2001)
• ISSN：1520-4995

文摘

Inositol monophosphatase (EC 3.1.3.25) in hyperthermophilic archaea is thought to play arole in the biosynthesis of di-myo-inositol-1,1'-phosphate (DIP), an osmolyte unique to hyperthermophiles.The Methanococcus jannaschii MJ109 gene product, the sequence of which is substantially homologousto that of human inositol monophosphatase, exhibits inositol monophosphatase activity but with substratespecificity that is broader than those of bacterial and eukaryotic inositol monophosphatases (it can alsoact as a fructose bisphosphatase). To understand its substrate specificity as well as the poor inhibition byLi⁺ (a potent inhibitor of the mammalian enzyme), we have crystallized the enzyme and determined itsthree-dimensional structure. The overall fold, as expected, is similar to that of the mammalian enzyme,but the details suggest a closer relationship to fructose 1,6-bisphosphatases. Three complexes of the MJ0109protein with substrate and/or product and inhibitory as well as activating metal ions suggest that thephosphatase mechanism is a three-metal ion assisted catalysis which is in variance with that proposedpreviously for the human inositol monophosphatase.