N-acetylgalactosamine kinase: A naturally promiscuous small molecule kinase

Helena Kristiansson, David J. Timson

Research output: Contribution to journalArticlepeer-review

Abstract

N-acetylgalactosamine kinase is a member of the GHMP family of small molecule kinases which catalyses the ATP-dependent phosphorylation of N-acetylgalactosamine. It is highly similar in structure and sequence to galactokinase. Alteration of galactokinase at a key tyrosine residue (Tyr-379 in the human enzyme) has been shown to dramatically enhance the substrate range of this enzyme. Here, we investigated the substrate specificity of the wild type N-acetylgalactosamine kinase and demonstrated that it can also catalyse the phosphorylation of N-acetylglucosamine and N-acetylmannosamine. In human N-acetylgalactosamine kinase, the equivalent residue to Tyr-379 in galactokinase is Phe-444. Alteration of this residue did not result in dramatic changes to the specificity of the enzyme. The more relaxed substrate specificity of N-acetylgalactosamine kinase, compared to galactokinase, can be explained by the greater flexibility of a glycine rich loop in the active site of the enzyme. These results suggest that N-acetylgalactosamine kinase is a potential biocatalyst for the phosphorylation of N-acetyl sugars. However, it is unlikely that it will be possible to further broaden the substrate range by alteration of Phe-444.

Original languageEnglish
Pages (from-to)57-63
Number of pages7
JournalApplied Biochemistry and Biotechnology
Volume166
Issue number1
DOIs
Publication statusPublished - 1 Jan 2012

Keywords

  • Biocatalysis
  • GALK2
  • GHMP kinase
  • N-acetyl sugar
  • Protein flexibility
  • Sugar phosphate

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