1s4e
From Proteopedia
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'''Pyrococcus furiosus galactokinase in complex with galactose, ADP and magnesium''' | '''Pyrococcus furiosus galactokinase in complex with galactose, ADP and magnesium''' | ||
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[[Category: Timson, D J.]] | [[Category: Timson, D J.]] | ||
[[Category: Verhees, C.]] | [[Category: Verhees, C.]] | ||
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Revision as of 05:16, 3 May 2008
Pyrococcus furiosus galactokinase in complex with galactose, ADP and magnesium
Overview
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.
About this Structure
1S4E is a Single protein structure of sequence from Pyrococcus furiosus. Full crystallographic information is available from OCA.
Reference
Substrate specificity and mechanism from the structure of Pyrococcus furiosus galactokinase., Hartley A, Glynn SE, Barynin V, Baker PJ, Sedelnikova SE, Verhees C, de Geus D, van der Oost J, Timson DJ, Reece RJ, Rice DW, J Mol Biol. 2004 Mar 19;337(2):387-98. PMID:15003454 Page seeded by OCA on Sat May 3 08:16:58 2008
