|The structure of LtaS as a rainbow-coloured cartoon with the |
electrostatic potential mapped to a semi-transparent surface. In the centre of the figure is the enzyme active site, with key amino acids picked out.
The latest de novo structure from Newcastle to be published is the lipoteichoic acid synthase, LtaS, from Bacillus subtilis. This enzyme is responsible for the synthesis of lipoteichoic acid, a chain of sugars attached to the cell membrane by a lipid anchor. These compounds are essential components of the cell wall of a sub-species of bacteria, called Gram-positive, whose cell walls lack the outer membrane found in Gram-negative bacteria. Lipoteichoic acid synthesis is required for the growth of the human pathogen Staphylococcus aureus and lipoteichoic acids have been shown to be essential factors in the regulation of cell-division in B. subtilis (Schirner et al, 2009). The LtaS structure reveals a phosphorylated amino acid in the enzyme active site, which instantly provides clues to the catalytic cycle.
“Teichoic acids are a vital component of the cell-wall of Gram-positive bacteria, helping to maintain the integrity of the cell and protecting the delicate cell-membrane from the environment, and playing a vital role in the bacterial life-cycle. Our results will enable a detailed understanding of the mechanism by which these teichoic acids are formed. This knowledge can be applied to the design of antibiotics against this key component of Gram-positive pathogens, including Staphylococcus aureus, the source of MRSA infections.”
Prof Richard Lewis, University of Newcastle-upon-Tyne
Distinct and essential morphogenic functions for wall- and lipoteichoic acids in Bacillus subtilis. K. Schirner; J. Marles-Wright; R. J. Lewis; J. Errington. EMBO J 2009, 28(7), 830-42.
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