Dynamic origins of substrate promiscuity in bacterial galactokinases.

Galactokinase catalyses the ATP-dependent phosphorylation of galactose and structurally related sugars. The enzyme has attracted interest as a potential biocatalyst for the production of sugar 1-phosphates and several attempts have been made to broaden its specificity. In general, bacterial galactokinases have wider substrate ranges than mammalian ones.

Modulation of the mobility of a key region in human galactokinase: Impacts on catalysis and stability.

Galactokinase catalyses the phosphorylation of α-d-galactose and some structurally related monosaccharides. The enzyme is of interest due to its potential as a biocatalyst for the production of sugar 1-phosphates and due to its involvement in the inherited metabolic disease type II galactosemia. It has been previously shown that a region (residues 231-245) in human galactokinase often has altered mobility when active site residues are varied.

A galactokinase-like protein from the liver fluke Fasciola hepatica.

Galactokinase catalyses the ATP-dependent phosphorylation of galactose. A galactokinase-like sequence was identified in a Fasciola hepatica EST library. Recombinant expression of the corresponding protein in Escherichia coli resulted in a protein of approximately 50 kDa.

Insight into the mechanism of galactokinase: Role of a critical glutamate residue and helix/coil transitions.

Galactokinase, the enzyme which catalyses the first committed step in the Leloir pathway, has attracted interest due to its potential as a biocatalyst and as a possible drug target in the treatment of type I galactosemia. The mechanism of the enzyme is not fully elucidated. Molecular dynamics (MD) simulations of galactokinase with the active site residues Arg-37 and Asp-186 altered predicted that two regions (residues 174-179 and 231-240) had different dynamics as a consequence.

Modulating Mobility: a Paradigm for Protein Engineering?

Proteins are highly mobile structures. In addition to gross conformational changes occurring on, for example, ligand binding, they are also subject to constant thermal motion. The mobility of a protein varies through its structure and can be modulated by ligand binding and other events.