1S4E

Pyrococcus furiosus galactokinase in complex with galactose, ADP and magnesium

Summary for 1S4E

• Entry DOI: 10.2210/pdb1s4e/pdb
• Descriptor: Galactokinase, alpha-D-galactopyranose, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: ghmp kinase superfamily, p-loop, transferase
• Biological source: Pyrococcus furiosus
• Total number of polymer chains: 9
• Total formula weight: 362219.40

Authors

Hartley, A.,Glynn, S.E.,Barynin, V.,Baker, P.J.,Sedelnikova, S.E.,Verhees, C.,de Geus, D.,van der Oost, J.,Timson, D.J.,Reece, R.J.,Rice, D.W. (deposition date: 2004-01-16, release date: 2004-04-06, Last modification date: 2024-04-03)

Primary citation

Hartley, A.,Glynn, S.E.,Barynin, V.,Baker, P.J.,Sedelnikova, S.E.,Verhees, C.,de Geus, D.,van der Oost, J.,Timson, D.J.,Reece, R.J.,Rice, D.W.
Substrate specificity and mechanism from the structure of Pyrococcus furiosus galactokinase
J.Mol.Biol., 337:387-398, 2004

PubMed Abstract: Galactokinase (GalK) catalyses the first step of the Leloir pathway of galactose metabolism, the ATP-dependent phosphorylation of galactose to galactose-1-phosphate. In man, defects in galactose metabolism can result in disorders with severe clinical consequences, and deficiencies in galactokinase have been linked with the development of cataracts within the first few months of life. The crystal structure of GalK from Pyrococcus furiosus in complex with MgADP and galactose has been determined to 2.9 A resolution to provide insights into the substrate specificity and catalytic mechanism of the enzyme. The structure consists of two domains with the active site in a cleft at the domain interface. Inspection of the substrate binding pocket identifies the amino acid residues involved in galactose and nucleotide binding and points to both structural and mechanistic similarities with other enzymes of the GHMP kinase superfamily to which GalK belongs. Comparison of the sequence of the Gal3p inducer protein, which is related to GalK and which forms part of the transcriptional activation of the GAL gene cluster in the yeast Saccharomyces cerevisiae, has led to an understanding of the molecular basis of galactose and nucleotide recognition. Finally, the structure has enabled us to further our understanding on the functional consequences of mutations in human GalK which cause galactosemia.

PubMed: 15003454
DOI: 10.1016/j.jmb.2004.01.043

Experimental method

X-RAY DIFFRACTION (2.9 Å)