Kinetic properties of Mycobacterium tuberculosis bifunctional GlmU

Arch Microbiol. 2011 Oct;193(10):751-7. doi: 10.1007/s00203-011-0715-8. Epub 2011 May 19.

Abstract

The UDP-N-acetylglucosamine (UDP-GlcNAc) is present as one of the glycosyl donors for disaccharide linker (D-N-GlcNAc-L-rhamnose) and the precursor of peptidoglycan in mycobacteria. The bifunctional enzyme GlmU involves in the last two sequential steps of UDP-GlcNAc synthetic pathway. Glucosamine-1-phosphate acetyltransferase catalyzes the formation of N-acetylglucosamine-1-phosphate (GlcNAc-1-P) from glucosamine-1-phosphate (GlcN-1-P) and acetyl coenzyme A (Acetyl CoA), and N-acetylglucosamine-1-phosphate uridyltransferase catalyzes the synthesis of UDP-GlcNAc from GlcNAc-1-P and UTP. The previous studies demonstrating the essentiality of GlmU to mycobacterial survival supported GlmU as a novel and potential target for TB drugs. In this work, two accurate and simple colorimetric assays based on 96-well microtiter plate were developed to measure the kinetic properties of bifunctional GlmU including initial velocity, optimal temperature, optimal pH, the effect of Mg2+, and the kinetic parameters. Both of the colorimetric assays for bifunctional GlmU enzyme activities and the kinetic properties will facilitate high-throughput screening of GlmU inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / metabolism
  • Bacterial Proteins / metabolism*
  • Colorimetry
  • Hydrogen-Ion Concentration
  • Kinetics
  • Magnesium / metabolism
  • Multienzyme Complexes / metabolism*
  • Mycobacterium tuberculosis / enzymology*
  • Nucleotidyltransferases / metabolism
  • Temperature

Substances

  • Bacterial Proteins
  • GlmU protein, Mycobacterium tuberculosis
  • Multienzyme Complexes
  • Acetyltransferases
  • glucosamine-1-phosphate acetyltransferase
  • Nucleotidyltransferases
  • UDPacetylglucosamine pyrophosphorylase
  • Magnesium