Office: SCIE 4250
Lab: SCIE 4205A
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:
1. Study of three types of bacterial aldolases that catalyze the same reaction on structurally similar substrates but are distinct evolutionarily (related by convergent evolution). These aldolases are part of aromatic degradation pathways that could be exploited for detoxification of industrial aromatic pollutants.
2. Cholesterol degradation in Mycobacterium tuberculosis. One third of the World’s population is thought to be 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.
- 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.
- Baker, P., Hillis, C., Carere, J. and Seah, S.Y.K. (2012) Protein-protein interactions and substrate channeling in orthologous and chimeric aldolase-dehydrogenase complexes. Biochemistry 51:1942-1952.
- Baker, P and Seah, S.Y.K. (2012) Rational Design of Stereoselectivity in the Class II Pyruvate Aldolase BphI. J Am Chem Soc. 134:507-513.
- Carere, J., Baker, P. and Seah, S.Y.K. (2011) Investigating the molecular determinants for substrate channeling in BphI-BphJ, an aldolase-dehydrogenase complex from the polychlorinated biphenyls degradation pathway. Biochemistry 50:8407-8416
- Baker, P., Carere, J. and Seah, S.Y.K. (2011) Probing the molecular basis of substrate specificity, stereospecificity, and catalysis in the class II pyruvate aldolase, BphI. Biochemistry 50:3559-3569.
- 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
- Wang, W., Mazurkewich, S., Kimber, M.S., and Seah, S.Y.K. (2010) Structural and kinetic characterization of 4-hydroxy-4-methyl-2-oxoglutarate (HMG)/4-carboxy-4-hydroxy-2-oxoadipate (CHA) aldolase: a protocatechuate degradation enzyme evolutionarily convergent with the HpaI and DmpG pyruvate aldolases. J. Biol. Chem. 285:36608-36615
Jason Carere (Ph.D.)
Scott Mazurkewich (Ph.D.)
Amanda Ruprecht (M.Sc.)