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Molecular structure of galactokinase.
James B Thoden1, Hazel M Holden
1Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
The Journal of Biological Chemistry
|June 11, 2003
Summary
We determined the 3D structure of galactokinase, an enzyme crucial for galactose metabolism. This structure reveals key residues involved in ligand binding and catalysis, providing insights into Type II galactosemia.
Area of Science:
- Biochemistry
- Structural Biology
- Enzymology
Background:
- Galactokinase (GALK) is essential for galactose metabolism, catalyzing the phosphorylation of alpha-D-galactose to galactose 1-phosphate.
- Mutations in the human GALK gene cause Type II galactosemia, a metabolic disorder.
Purpose of the Study:
- To elucidate the three-dimensional structure of galactokinase from Lactococcus lactis.
- To provide a structural basis for understanding GALK function and the molecular basis of Type II galactosemia.
Main Methods:
- X-ray crystallography was used to determine the 3D structure of galactokinase.
- The structure was solved to a resolution of 2.1 Å in the presence of alpha-D-galactose and inorganic phosphate.
Main Results:
- Galactokinase exhibits a topology similar to other GHMP superfamily members, with distinct N-terminal and C-terminal beta-sheet domains.
- Alpha-D-galactose and inorganic phosphate ligands bind between these domains, interacting with conserved residues Arg36 and Asp183.
- These conserved residues are proposed to play critical roles in the enzyme's catalytic mechanism.
Conclusions:
- The determined galactokinase structure provides a molecular model for enzyme function.
- This structural information can aid in understanding the impact of mutations leading to Type II galactosemia in humans.