Download MendeleyCrystal structure and catalytic mechanism of the MJ0109 gene product: a bifunctional enzyme with inositol monophosphatase and fructose 1,6-bisphosphatase activities.
Johnson, K.A., Chen, L., Yang, H., Roberts, M.F., Stec, B.(2001) Biochemistry 40: 618-630
- PubMed: 11170378
- DOI: https://doi.org/10.1021/bi0016422
- Primary Citation of Related Structures:
1G0H, 1G0I - PubMed Abstract:
Inositol monophosphatase (EC 3.1.3.25) in hyperthermophilic archaea is thought to play a role 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 homologous to that of human inositol monophosphatase, exhibits inositol monophosphatase activity but with substrate specificity that is broader than those of bacterial and eukaryotic inositol monophosphatases (it can also act as a fructose bisphosphatase). To understand its substrate specificity as well as the poor inhibition by Li(+) (a potent inhibitor of the mammalian enzyme), we have crystallized the enzyme and determined its three-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 MJ0109 protein with substrate and/or product and inhibitory as well as activating metal ions suggest that the phosphatase mechanism is a three-metal ion assisted catalysis which is in variance with that proposed previously for the human inositol monophosphatase.
Organizational Affiliation:
Department of Biochemistry and Cell Biology, W. M. Keck Center for Computational Biology, Rice University, Houston, Texas 77005, USA.
