Toward a structural understanding of the dehydratase mechanism

S T M Allard, K Beis, M F Giraud, A D Hegeman, J W Gross, R C Wilmouth, C Whitfield, M Graninger, P Messner, A G Allen, D J Maskell, Jim Naismith

Research output: Contribution to journalArticlepeer-review

79 Citations (Scopus)

Abstract

dTDP-D-glucose 4,6-dehydratase (RmIB) was first identified in the L-rhamnose biosynthetic pathway, where it catalyzes the conversion of dTDP-D-glucose into dTDP-4-keto-6-deoxy-D-glucose. The structures of RmIB from Salmonella enterica serovar Typhimurium in complex with substrate deoxythymidine 5'-diphospho-D-glucose (dTDP-D-glucose) and deoxythymidine 5'-diphosphate (dTDP), and RmIB from Streptococcus suis serotype 2 in complex with dTDP-D-glucose, dTDP, and deoxythymidine 5'-diphospho-D-pyrano-xylose (dTDP-xylose) have all been solved at resolutions between 1.8 Angstrom and 2.4 Angstrom. The structures show that the active sites are highly conserved. Importantly, the structures show that the active site tyrosine functions directly as the active site base, and an aspartic and glutamic acid pairing accomplishes the dehydration step of the enzyme mechanism. We conclude that the substrate is required to move within the active site to complete the catalytic cycle and that this movement is driven by the elimination of water. The results provide insight into members of the SDR superfamily.

Original languageEnglish
Pages (from-to)81-92
Number of pages12
JournalStructure
Volume10
Issue number1
DOIs
Publication statusPublished - Jan 2002

Keywords

  • UDP-GALACTOSE 4-EPIMERASE
  • ENTERICA SEROVAR TYPHIMURIUM
  • RHAMNOSE SYNTHESIS PATHWAY
  • ESCHERICHIA-COLI
  • MACROMOLECULAR STRUCTURES
  • GLUCOSE 4,6-DEHYDRATASE
  • ENZYMATIC CATALYSIS
  • STREPTOCOCCUS-SUIS
  • CRYSTAL-STRUCTURE
  • BIOSYNTHESIS

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