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 journalArticle

11 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

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

Fingerprint Dive into the research topics of 'Dynamic elements govern the catalytic activity of CapE, a capsular polysaccharide-synthesizing enzyme from Staphylococcus aureus'. Together they form a unique fingerprint.

  • Cite this