I have always been fascinated by how proteins, made up of simple building blocks of 20 amino acids, could serve the diverse functions required in living systems. I have previously worked with Reiske iron-sulphur proteins (M.Sc. research), phenylalanine dehydrogenase (Ph.D. research) and C-C bond cleaving hydrolases (Postdoctoral work in Université Laval and University of British Columbia). In Guelph, my lab is studying enzymes related by convergent and divergent evolution to decipher structure-function relationships in proteins. Target enzymes being investigated include those important for environmental pollutant degradation and those that are medically relevant for development of new therapeutic drugs.
B.Sc. National University of Singapore
M.Sc. National University of Singapore
Ph.D. University of Sheffield, UK
We employ a variety of interdisciplinary techniques in our research, including molecular genetics, site-specific mutagenesis, protein purification, various spectroscopic methods and structural biology. Current research projects include:
- Steroid degradation in Mycobacterium tuberculosis and other bacteria.
One third of the World's population is infected with Mycobacterium tuberculosis and about 10% of these individuals will develop tuberculosis during their lifetime. The emergence of drug resistant strains of M. tuberculosis, including the recent report of individuals infected with TDR-TB (totally drug resistant M. tuberculosis), has raised concerns that the currently used antibiotics may be insufficient to contain the disease. The cholesterol degradation pathway in M. tuberculosis is important for the persistence of the bacteria in host macrophages, and it therefore represents a potential target for development of new antibiotics against this pathogen.
- Study of microbial enzymes involved in degradation of plant biomass (Lignin) and aromatic environmental pollutants.
- Ruprecht, A., Maddox, J., Stirling, A.J., Visaggio, N. and Seah S..Y.K. (2015) Characterization of novel Acyl-CoA dehydrogenases involved in bacterial steroid degradation. J. Bacteriol. 197:1360-1367
- Mazurkewich, S., Wang, W. and Seah S.Y.K. (2014) Biochemical and structural analysis of RraA proteins to decipher their relationships with 4-hydroxy-4-methyl-2-oxoglutarate/4-carboxy-4-hydroxy-2-oxoadipate aldolases. Biochemistry 53:542-553
- Carere, J., McKenna, S.E., Kimber, M.S. and Seah S.Y.K. (2013) Characterization of an Aldolase-Dehydrogenase Complex from the Cholesterol Degradation Pathway of Mycobacterium tuberculosis. Biochemistry 52:3502-3511.
- Coincon, M., Wang, W., Sygusch, J., Seah S.Y.K. (2012) Crystal Structure of Reaction Intermediates in Pyruvate Class II Aldolase: Substrate cleavage, enolate stabilization, and substrate specificity. Coincon M, Wang W, Sygusch J, Seah SY. J Biol Chem. 287:36208-36221
- Baker, P., Carere, J. and Seah, S.Y.K. (2012) Substrate Specificity, Substrate Channeling, and Allostery in BphJ: An Acylating Aldehyde Dehydrogenase Associated with the Pyruvate Aldolase BphI. Biochemistry 51:4558-4567.
- Ng, F.S.W., Wright, D. and Seah, S.Y.K. (2011) Characterization of a phosphotriesterase-like lactonase from Sulfolobus solfataricus and its immobilization for quorum quenching. Appl Environ Microbiol 77:1181-1186
Scott Mazurkewich (Ph.D.)
Alexander (AJ) Stirling (M.Sc.)
Stephanie Gilbert (M.Sc.)
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