PDBsum entry 4x7r

Transferase

PDB id: 4x7r

Contents

Protein chains

493 a.a.

Ligands

ZDO-IDS-SUS-BDP-SGN ×2

UDP ×2

3YW ×2

Waters ×365

References listed in PDB file

Key reference

• Title: Structure and mechanism of staphylococcus aureus tarm, The wall teichoic acid α-Glycosyltransferase.
• Authors: S.Sobhanifar, L.J.Worrall, R.J.Gruninger, G.A.Wasney, M.Blaukopf, L.Baumann, E.Lameignere, M.Solomonson, E.D.Brown, S.G.Withers, N.C.Strynadka.
• Ref.: Proc Natl Acad Sci U S A, 2015, 112, E576. [DOI no: 10.1073/pnas.1418084112]
• PubMed id: 25624472

Abstract

Unique to Gram-positive bacteria, wall teichoic acids are anionic glycopolymers cross-stitched to a thick layer of peptidoglycan. The polyol phosphate subunits of these glycopolymers are decorated with GlcNAc sugars that are involved in phage binding, genetic exchange, host antibody response, resistance, and virulence. The search for the enzymes responsible for GlcNAcylation in Staphylococcus aureus has recently identified TarM and TarS with respective α- and β-(1-4) glycosyltransferase activities. The stereochemistry of the GlcNAc attachment is important in balancing biological processes, such that the interplay of TarM and TarS is likely important for bacterial pathogenicity and survival. Here we present the crystal structure of TarM in an unusual ternary-like complex consisting of a polymeric acceptor substrate analog, UDP from a hydrolyzed donor, and an α-glyceryl-GlcNAc product formed in situ. These structures support an internal nucleophilic substitution-like mechanism, lend new mechanistic insight into the glycosylation of glycopolymers, and reveal a trimerization domain with a likely role in acceptor substrate scaffolding.