Dr Lindsay Sawyer's Research Group
Research Activities:
Background
The principal research interest of my group is the relationship between the structure and function of biological macromolecules, particularly proteins. Not only does this involve determining the structures of a variety of proteins for their own intrinsic scientific interest - what do they do, how do they do it, predicting from site-directed mutagenesis the effects on both the structure and properties - but also in trying to integrate the behaviour of the protein into its wider metabolic/physiological context. The main technique employed is X-ray crystallography, the main method that leads to an accurate atomic picture of a large molecule. Kinetic, binding and chemical modification studies are also undertaken in order to complement the structural work.
My major contribution is in two areas:
Studies of Binding Proteins
First, a study of binding proteins, in particular the milk protein beta-lactoglobulin, a lipocalin that has involved collaborations with throughout the world. The structural work is now fundamental to the design of stability experiments important to the dairy industry, but also there is a potential application in flavour control. The recent award of JIF funding to establish the Centre for Science at Extreme Conditions (CSEC) has further extended work on binding proteins through collaboration with Doug Bartlett (Scripps Oceanography) on proteins from piezophiles (organisms that live at high hydrostatic pressures), and this is set to expand further into comparisons of piezophilic enzyme activities - see below. We are currently determining the pressure dependence of the ligand binding.
Enzyme Mechanism
The second focus is enzyme mechanism and highly productive collaborations with Bob Baxter and Dominic Campopiano (Chemistry), John Coggins (Glasgow), Alastair Hawkins (Newcastle) have produced structures of 4 key enzymes together with a number of substrate, substrate-analogue- and inhibitor-bound structures.
Research Figure:
Figure Legend:
Bovine beta-lactoglobulin showing the internal binding site. Also shown are palmitic acid (blue) and cholesterol (green), from the results of two separate binding studies.
Selected Publications:
D.Gourley, A.K.Shrive, I. Polikarpov, T. Krell, J.R.Coggins, A.R.Hawkins and L. Sawyer. (1999) Two enzymes, one reaction - the 3-dimensional structures of Types I and II 3-dehydroquinase. Nature Structure Biology: 6: (521-525)
S.P.Webster, D.Alexeev, D.J.Campopiano, R.M.Watt, M.Alaxeeva, L.J.Mullan, L.Sawyer and R.L.Baxter (2000) Spectroscopic and crystallographic characterisation of key intermediates in the PLP-mediated catalytic pathway of Escherichia coli 8-amino-7-oxononano
G.Kontopidis, C.Holt and L.Sawyer (2002) Retinol binding to bovine beta-lactoglobulin. J.Mol.Biol: 318: (1043-1055)
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