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Title: Structure of the E. Coli Bifunctional GlmU Acetyltransferase Active Site with Substrates and Products

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{sub 4} to form GlcNAc-1-PO{sub 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{sub 4}, and desulpho-CoA/GlcNAc-1-PO{sub 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{sub 4} is positioned in proximity to the acetyl-CoA to facilitate direct attack on its thioester by a ternary complex mechanism.

Authors:
; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
929913
Report Number(s):
BNL-80498-2008-JA
TRN: US200822%%1087
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Protein Science; Journal Volume: 16
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; ACETYLATION; BACTERIA; BIOSYNTHESIS; COMPLEXES; CRYSTAL STRUCTURE; ENZYMES; ESCHERICHIA COLI; LIPOPOLYSACCHARIDES; POTENTIALS; PYROPHOSPHATES; SUBSTRATES; UTP; national synchrotron light source

Citation Formats

Olsen,L., Vetting, M., and Roderick, S. Structure of the E. Coli Bifunctional GlmU Acetyltransferase Active Site with Substrates and Products. United States: N. p., 2007. Web. doi:10.1110/ps.072779707.
Olsen,L., Vetting, M., & Roderick, S. Structure of the E. Coli Bifunctional GlmU Acetyltransferase Active Site with Substrates and Products. United States. doi:10.1110/ps.072779707.
Olsen,L., Vetting, M., and Roderick, S. Mon . "Structure of the E. Coli Bifunctional GlmU Acetyltransferase Active Site with Substrates and Products". United States. doi:10.1110/ps.072779707.
@article{osti_929913,
title = {Structure of the E. Coli Bifunctional GlmU Acetyltransferase Active Site with Substrates and Products},
author = {Olsen,L. and Vetting, M. and Roderick, S.},
abstractNote = {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{sub 4} to form GlcNAc-1-PO{sub 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{sub 4}, and desulpho-CoA/GlcNAc-1-PO{sub 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{sub 4} is positioned in proximity to the acetyl-CoA to facilitate direct attack on its thioester by a ternary complex mechanism.},
doi = {10.1110/ps.072779707},
journal = {Protein Science},
number = ,
volume = 16,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}
  • No abstract prepared.
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