Getting a better understanding of molecular mechanisms

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.

Researchers at Newcastle University’s Institute for Cell and Molecular Biosciences are regular users of Diamond’s MX beamlines. One of the complications of crystallography is that part of the information required to determine structures is lost in the diffraction experiment. This information can be inferred in special circumstances in a ‘SAD’ (single-wavelength anomalous dispersion) experiment. In common with other MX users, the Newcastle group have been utilising these SAD experiments to obtain a better understanding of biological mechanisms at the molecular level. The Newcastle group have elucidated a series of structure solutions, including eight SAD structure determinations, between November 2007 and February 2009.

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.

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.