4X7M

Crystal structure of S. aureus TarM G117R mutant in complex with UDP and UDP-GlcNAc

Summary for 4X7M

• Entry DOI: 10.2210/pdb4x7m/pdb
• Related: 4X6L 4X7P 4X7R
• Descriptor: TarM, URIDINE-5'-DIPHOSPHATE, URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE, ... (4 entities in total)
• Functional Keywords: glycosyltransferase gt-b retaining wall teichoic acid, transferase
• Biological source: Staphylococcus aureus subsp. aureus 21178
• Total number of polymer chains: 2
• Total formula weight: 115939.19

Authors

Worrall, L.J.,Sobhanifar, S.,Strynadka, N.C. (deposition date: 2014-12-09, release date: 2015-03-04, Last modification date: 2024-02-28)

Primary citation

Sobhanifar, S.,Worrall, L.J.,Gruninger, R.J.,Wasney, G.A.,Blaukopf, M.,Baumann, L.,Lameignere, E.,Solomonson, M.,Brown, E.D.,Withers, S.G.,Strynadka, N.C.
Structure and mechanism of Staphylococcus aureus TarM, the wall teichoic acid alpha-glycosyltransferase.
Proc.Natl.Acad.Sci.USA, 112:E576-E585, 2015

PubMed 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.

PubMed: 25624472
DOI: 10.1073/pnas.1418084112

Experimental method

X-RAY DIFFRACTION (2.4 Å)