Abstract
The role of ribokinase-like carbohydrate kinases consists in ATP dependent phosphorylation of small molecules containing hydroxymethyl group. Although they differ substantially in structural terms and exhibit a broad substrate specificity, some family-wide conserved features can be distinguished suggesting the common mode of action. 4-methyl-5-β-hydroxyethylthiazole kinase (Thz kinase) was chosen as a representative model and the mechanism proposed in X-ray crystal structure paper provided the basis for calculations. In particular, the possible role of several active site residues (Arg121 and Cys198 among others) and of the two magnesium ions was examined. Static and dynamic catalytic fields for the reaction were generated revealing the most favourable environment for the preferential transition state stabilization. An attempt to model the phosphoryl transfer reaction as well as to investigate the influence of the cysteine residue on the reaction course at the semiempirical PM3 level of theory was undertaken.
Highlights
Structure of Bacillus subtilis YXKO – hypothetical protein with unknown function obtained recently in Structural Genomics project [1], revealed structural homology to ribokinase-like family of carbohydrate kinases (RK-kinases) and raised some questions about catalytic mechanism.Kinases are a ubiquitous group of enzymes that facilitates phosphoryl transfer reaction fromInt
An existence of a set of conserved water molecules was reported, for example, in case of protein kinase A [28], where comparison of known crystal structures revealed the presence of six structured water molecules interacting with ATP, two magnesium ions and such an active site residues as aspartate, glutamate or lysine
The optimized distances between water molecules oxygen atoms and magnesium ions are similar to that proposed for protein kinase A, the contacts made by Mg2+ and coordinated phosphate oxygen atoms (1.8Å) are too close
Summary
Structure of Bacillus subtilis YXKO – hypothetical protein with unknown function obtained recently in Structural Genomics project [1], revealed structural homology to ribokinase-like family of carbohydrate kinases (RK-kinases) and raised some questions about catalytic mechanism.Kinases are a ubiquitous group of enzymes that facilitates phosphoryl transfer reaction fromInt. Structure of Bacillus subtilis YXKO – hypothetical protein with unknown function obtained recently in Structural Genomics project [1], revealed structural homology to ribokinase-like family of carbohydrate kinases (RK-kinases) and raised some questions about catalytic mechanism. Kinases are a ubiquitous group of enzymes that facilitates phosphoryl transfer reaction from. 2004, 5 142 a phosphate donor (usually ATP) to an acceptor substrate. The largest and the most extensively studied is the family of protein kinases, but other groups of kinases, neither so well characterized nor investigated, exhibit very interesting features
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