Crystal structure of the capsular polysaccharide synthesizing protein CapE of Staphylococcus aureus

Takamitsu Miyafusa, Jose Manuel Martinez Caaveiro, Yoshikazu Tanaka, Martin E. Tanner, Kouhei Tsumoto

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Enzymes synthesizing the bacterial CP (capsular polysaccharide) are attractive antimicrobial targets. However, we lack critical information about the structure and mechanism of many of them. In an effort to reduce that gap, we have determined three different crystal structures of the enzyme CapE of the human pathogen Staphylococcus aureus. The structure reveals that CapE is a member of the SDR (short-chain dehydrogenase/reductase) super-family of proteins. CapE assembles in a hexameric complex stabilized by three major contact surfaces between protein subunits. Turnover of substrate and/or coenzyme induces major conformational changes at the contact interface between protein subunits, and a displacement of the substrate-binding domain with respect to the Rossmann domain. A novel dynamic element that we called the latch is essential for remodelling of the protein-protein interface. Structural and primary sequence alignment identifies a group of SDR proteins involved in polysaccharide synthesis that share the two salient features of CapE: the mobile loop (latch) and a distinctive catalytic site (MxxxK). The relevance of these structural elements was evaluated by site-directed mutagenesis.

Original languageEnglish
Article numbere00043
Pages (from-to)463-474
Number of pages12
JournalBioscience reports
Volume33
Issue number3
DOIs
Publication statusPublished - Jul 8 2013

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Polysaccharides
Staphylococcus aureus
Oxidoreductases
Crystal structure
Protein Subunits
Proteins
Bacterial Polysaccharides
Mutagenesis
Sequence Alignment
Coenzymes
Pathogens
Substrates
Enzymes
Site-Directed Mutagenesis
Catalytic Domain
Membrane Proteins
short chain trans-2-enoyl-CoA reductase

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Crystal structure of the capsular polysaccharide synthesizing protein CapE of Staphylococcus aureus. / Miyafusa, Takamitsu; Martinez Caaveiro, Jose Manuel; Tanaka, Yoshikazu; Tanner, Martin E.; Tsumoto, Kouhei.

In: Bioscience reports, Vol. 33, No. 3, e00043, 08.07.2013, p. 463-474.

Research output: Contribution to journalArticle

Miyafusa, Takamitsu ; Martinez Caaveiro, Jose Manuel ; Tanaka, Yoshikazu ; Tanner, Martin E. ; Tsumoto, Kouhei. / Crystal structure of the capsular polysaccharide synthesizing protein CapE of Staphylococcus aureus. In: Bioscience reports. 2013 ; Vol. 33, No. 3. pp. 463-474.
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