Dynamic elements govern the catalytic activity of CapE, a capsular polysaccharide-synthesizing enzyme from Staphylococcus aureus

Takamitsu Miyafusa, Jose M.M. Caaveiro, Yoshikazu Tanaka, Kouhei Tsumoto

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

CapE is an essential enzyme for the synthesis of capsular polysaccharide (CP) of pathogenic strains of Staphylococcus aureus. Herein we demonstrate that CapE is a 5-inverting 4,6-dehydratase enzyme. However, in the absence of downstream enzymes, CapE catalyzes an additional reaction (5-back-epimerization) affording a by-product under thermodynamic control. Single-crystal X-ray crystallography was employed to identify the structure of the by-product. The structural analysis reveals a network of coordinated motions away from the active site governing the enzymatic activity of CapE. A second dynamic element (the latch) regulates the enzymatic chemoselectivity. The validity of these mechanisms was evaluated by site-directed mutagenesis.

Original languageEnglish
Pages (from-to)3824-3830
Number of pages7
JournalFEBS Letters
Volume587
Issue number23
DOIs
Publication statusPublished - 2013 Nov 29
Externally publishedYes

Keywords

  • Capsular polysaccharide
  • Conformational change
  • Pathogenic bacterium
  • SDR enzyme
  • Staphylococcus aureus
  • UDP-sugar
  • X-ray crystallography

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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