Structure of the E. coli bifunctional GlmU acetyltransferase active site with substrates and products
- 1 June 2007
- journal article
- Published by Wiley in Protein Science
- Vol. 16 (6), 1230-1235
- https://doi.org/10.1110/ps.072779707
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-PO(4) to form GlcNAc-1-PO(4) 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-PO(4), and desulpho-CoA/GlcNAc-1-PO(4). 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-PO(4) is positioned in proximity to the acetyl-CoA to facilitate direct attack on its thioester by a ternary complex mechanism.Keywords
This publication has 20 references indexed in Scilit:
- Crystal Structure of Streptococcus pneumoniae N-Acetylglucosamine-1-phosphate Uridyltransferase Bound to Acetyl-coenzyme A Reveals a Novel Active Site ArchitecturePublished by Elsevier BV ,2001
- Structure of the Escherichia coli GlmU Pyrophosphorylase and Acetyltransferase Active Sites,Biochemistry, 2001
- Crystal Structures of Streptococcus pneumoniaeN-Acetylglucosamine-1-phosphate Uridyltransferase, GlmU, in Apo Form at 2.33Å Resolution and in Complex with UDP-N-Acetylglucosamine and Mg2+ at 1.96Å ResolutionJournal of Molecular Biology, 2001
- Crystal structure of the bifunctional N-acetylglucosamine 1-phosphate uridyltransferase from Escherichia coli: a paradigm for the related pyrophosphorylase superfamilyThe EMBO Journal, 1999
- [20] Processing of X-ray diffraction data collected in oscillation modeMethods in Enzymology, 1997
- Acetyltransfer Precedes Uridylyltransfer in the Formation of UDP-N-acetylglucosamine in Separable Active Sites of the Bifunctional GlmU Protein of Escherichia coliBiochemistry, 1996
- Eight bacterial proteins, including UDP-N-acetylglucosamine acyltransferase (LpxA) and three other transferases of Escherichia coli, consist of a six-residue periodicity themeFEMS Microbiology Letters, 1992
- Eight bacterial proteins, including UDP-N-acetylglucosamine acyltransferase (LpxA) and three other transferases ofEscherichia coli, consist of a six-residue periodicity themeFEMS Microbiology Letters, 1992
- What is known about the structure and function of the Escherichia coli protein FirA?Molecular Microbiology, 1992
- Improved methods for building protein models in electron density maps and the location of errors in these modelsActa Crystallographica Section A Foundations of Crystallography, 1991