The crystal structure of the Y140F mutant of ADP-L-glycero-D-manno-heptose 6-epimerase bound to ADP-beta-D-mannose suggests a one base mechanism

Thomas Kowatz, James P. Morrison, Martin E. Tanner, Jim Naismith

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)
1 Downloads (Pure)

Abstract

Bacteria synthesize a wide array of unusual carbohydrate molecules, which they use in a variety of ways. The carbohydrate L-glycero-D-manno-heptose is an important component of lipopolysaccharide and is synthesized in a complex series of enzymatic steps. One step involves the epimerization at the C6 '' position converting ADP-D-glycero-D-manno-heptose into ADP-L-glycero-D-manno-heptose. The enzyme responsible is a member of the short chain dehydrogenase superfamily, known as ADP-L-glycero-D-manno-heptose 6-epimerase (AGME). The structure of the enzyme was known but the arrangement of the catalytic site with respect to the substrate is unclear. We now report the structure of AGME bound to a substrate mimic, ADP-beta-D-mannose, which has the same stereochemical configuration as the substrate. The complex identifies the key residues and allows mechanistic insight into this novel enzyme.

Original languageEnglish
Pages (from-to)1337-1343
Number of pages7
JournalProtein Science
Volume19
Issue number7
Early online date5 May 2010
DOIs
Publication statusPublished - Jul 2010

Keywords

  • LPS biosynthesis
  • Hydride transfer
  • Keto sugar
  • Carbohydrate
  • SDR enzymes
  • Short-chain dehydrogenases/reductases
  • Udp-galactose 4-epimerase
  • D-mannoheptose 6-epimerase
  • Escherichia-coli
  • RFAD gene
  • Binding
  • Biosynthesis
  • Catalysis
  • Pathway

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