Synopsis
Enzymes synthesizing the bacterial capsular polysaccharide (CP) 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 short-chain  dehydrogenase/reductase (SDR) 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 remodeling 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.

This Article was published in Bioscience Reports and is free to access.