Structure of the E. coli bifunctional GlmU acetyltransferase active site with substrates and products

Laurence R. Olsen, Matthew W. Vetting, Steven L. Roderick

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

The biosynthesis of UDP-GlcNAc in bacteria is carried out by GlmU, an essential bifunctional uridyltransferase that catalyzes the CoA-dependent acetylation of GlcN-1-PO4 to form GlcNAc-1-PO4 and its subsequent condensation with UTP to form pyrophosphate and UDP-GlcNAc. As a metabolite, UDP-GlcNAc is situated at a branch point leading to the biosynthesis of lipopolysaccharide and peptidoglycan. Consequently, GlmU is regarded as an important target for potential antibacterial agents. The crystal structure of the Escherichia coli GlmU acetyltransferase active site has been determined in complexes with acetyl-CoA, CoA/GlcN-1-PO4, and desulpho-CoA/GlcNAc-1- PO4. These structures reveal the enzyme groups responsible for binding the substrates. A superposition of these complex structures suggests that the 2-amino group of GlcN-1-PO4 is positioned in proximity to the acetyl-CoA to facilitate direct attack on its thioester by a ternary complex mechanism. Published by Cold Spring Harbor Laboratory Press.

Original languageEnglish (US)
Pages (from-to)1230-1235
Number of pages6
JournalProtein Science
Volume16
Issue number6
DOIs
Publication statusPublished - Jun 1 2007

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Keywords

  • Acetyltransferase
  • Coenzyme A
  • Lipopolysaccharide
  • Peptidoglycan
  • Pyrophosphorylase
  • UDP-N-acetylglucosamine
  • Uridyltransferase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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