Proteins carry out complex chemical transformations that remain beyond the reach of synthetic methods. Not only that they do so efficiently in water and with no waste solvents. We are very interested in figuring out how enzymes carry out reactions. To do this we often start by solving the structure of the protein then following up with molecular biology, enzyme assay, spectroscopic approaches, HPLC analysis of products and mass spectroscopic methods. We define catalysis in broad terms and have recently worked on n protein which takes a large carbohydrate polymer and transports it across the membrane. This is a very difficult kinetic process, as the bacterial outer membrane is very hydrophobic. We are increasingly interested in such membrane proteins. However, we have a strong interest in unusual metabolites for example pyrrolnitrin pathway.

Two views of Wza, a protein which exports the polysaccharide that forms the capsule required for infection by pathogenic bacteria. The protein weighs 340,000 amu and measures over 150Å x 100Å x 100Å	The pyrrolnitirin biosynthetic pathway has a number of unusual chemical steps. The study of PrnA has revealed a new mechanism for halogenation.

SELECTED RECENT PUBLICATIONS

1. Dong, C., Beis, K., Nesper, J., Brunkan, A.L., Clarke, B.R., Whitfield, C. & Naismith, J.H. (2006) Wza the translocon for E. coli capsular polysaccharides is a new class of membrane protein. Nature, In press
2. Naismith, J.H. (2006) Inferring the chemical mechanism from structures of enzymes. Chem. Soc. Reviews 36, 763-770
3. Major, L.L., Woluka, B & Naismith, J.H. (2005) Structure and function of GDP-mannose-3' ,5' -epimerase; an enzyme which performs three chemical reactions at the same active site. J. Amer. Chem. Soc. 127, 18309-18320
4. Dong C., Flecks S., Unversucht S., Haupt C., Van Pee, K-H., & Naismith J.H.^ (2005) The structure of tryptophan 7-halogenase (PrnA) suggests a mechanism for regioselective chlorination. Science, 309, 2216-2219
5. Williams GJ, Breazeale SD, Raetz CR & Naismith JH. (2005) Structure and function of both domains of ArnA, a dual function decarboxylase and a formyltransferase, involved in 4-amino-4-deoxy-L-arabinose biosynthesis. J Biol Chem. 280, 23000-23008
6. Dong, C, Huang, FL, Deng, H, Schaffrath, C, Spencer, JB, O’Hagan, D & Naismith, JH (2004) Crystal structure and mechanism of a bacterial fluorinating enzyme. Nature, 427, 561-565
7. Beis, K., Allard, S.T.M., Hegeman, A.D., Murshudov, G., Philp, D., & Naismith, J.H. (2003) The structure of NADH in the enzyme dTDP-D-glucose dehydratase (RmlB). J. Amer. Chem Soc., 125:11872-8