1pie
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Crystal Structure of Lactococcus lactis Galactokinase Complexed with Galactose
OverviewOverview
Galactokinase plays a key role in normal galactose metabolism by, catalyzing the ATP-dependent phosphorylation of alpha-D-galactose to, galactose 1-phosphate. In humans, mutations in the galactokinase gene can, lead to the diseased state referred to as Type II galactosemia. Here we, describe the three-dimensional structure of galactokinase from Lactococcus, lactis determined to 2.1-A resolution. As expected from amino acid, sequence alignments, galactokinase adopts a similar topology to that, observed for members of the GHMP superfamily. The N-terminal domain is, characterized by a five-stranded mixed beta-sheet while the C-terminal, motif is dominated by two distinct four-stranded anti-parallel, beta-sheets. The structure was solved in the presence of alpha-D-galactose, and inorganic phosphate. These ligands are wedged between the N- and, C-terminal domains. Amino acid side chains responsible for anchoring the, sugar ligand to the protein include Arg36, Glu42, Asp45, Asp183, and, Tyr233. Both Arg36 and Asp183 are strictly conserved in the amino acid, sequences available in the literature thus far for galactokinases., Interestingly, the carboxylate side chain of Asp183 is positioned within, 3.5 A of the C-1 hydroxyl group of galactose, whereas the guanidinium, group of Arg36 is situated between both the C-1 hydroxyl group and the, inorganic phosphate. Most likely these residues play key roles in, catalysis. The structure of galactokinase described here serves as a model, for understanding the functional consequences of point mutations known to, result in Type II galactosemia in humans.
About this StructureAbout this Structure
1PIE is a Single protein structure of sequence from Lactococcus lactis with GLA and PO4 as ligands. Active as Galactokinase, with EC number 2.7.1.6 Full crystallographic information is available from OCA.
ReferenceReference
Molecular structure of galactokinase., Thoden JB, Holden HM, J Biol Chem. 2003 Aug 29;278(35):33305-11. Epub 2003 Jun 9. PMID:12796487
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