Structure of the Bacillus anthracis dTDP- l -rhamnose-biosynthetic enzyme dTDP-4-dehydrorhamnose reductase (RfbD)

Ashley Law, Alexander Stergioulis, Andrei S. Halavaty, George Minasov, Wayne F. Anderson, Misty L. Kuhn*

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Bacillus anthracis is the causative agent of the deadly disease Anthrax. Its use in bioterrorism and its ability to re-emerge have brought renewed interest in this organism. B. anthracis is a Gram-positive bacterium that adds l-rhamnose to its cell-wall polysaccharides using the activated donor dTDP-β-l-rhamnose. The enzymes involved in the biosynthesis of the activated donor are absent in humans, which make them ideal targets for therapeutic development to combat pathogens. Here, the 2.65 Å resolution crystal structure of the fourth enzyme in the dTDP-β-l-rhamnose-biosynthetic pathway from B. anthracis, dTDP-4-dehydro-β-l-rhamnose reductase (RfbD), is presented in complex with NADP+. This enzyme catalyzes the reduction of dTDP-4-dehydro-β-l-rhamnose to dTDP-β-l-rhamnose. Although the protein was co-crystallized in the presence of Mg2+, the protein lacks the conserved residues that coordinate Mg2+.The crystal structure of dTDP-4-dehydro-β-l-rhamnose reductase (RfbD) from Bacillus anthracis was determined at 2.65 Å resolution in complex with NADP+. RfbD is the fourth enzyme of the dTDP-β-l-rhamnose-biosynthetic pathway and provides evidence that RfbD homologs in Gram-positive bacteria exhibit key differences in the residues important for oligomerization and metal utilization compared with those from many Gram-negative bacteria.

Original languageEnglish (US)
Pages (from-to)644-650
Number of pages7
JournalActa Crystallographica Section F:Structural Biology Communications
Volume73
Issue number12
DOIs
StatePublished - Dec 2017

Keywords

  • Anthrax
  • Bacillus anthracis
  • RfbD
  • dTDP-4-dehydrorhamnose reductase

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Genetics
  • Condensed Matter Physics

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