Email: sseah@uoguelph.ca

Office: SCIE 4250
Ext: 56750
Lab: SCIE 4205A
Ext: 53026

Profile

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.

Education

B.Sc. National University of Singapore
M.Sc. National University of Singapore
Ph.D. University of Sheffield, UK

Research

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 or could be used to develop new antibiotics against bacterial pathogens, such as Mycobacterium tuberculosis.

2.  Structure-function studies of phosphotriesterases/lactonases. These bifunctional enzymes have the ability to hydrolyze organophosphate pesticides/nerve agenets and bacterial quorum sensing molecules (N-acyl homoserine lactones). We are developing these enzymes as biosensors for detecting pesticide residues in food and as a system to attenuate bacterial virulence by disrupting quorum sensing. 

Selected Publications

  1. 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
  2. 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
  3. 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.
  4. 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
  5. 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
  6. Wang, W., Baker, P. and Seah, S.Y.K. (2010) Comparison of two metal-dependent pyruvate aldolases related by convergent evolution: substrate specificity, kinetic mechanism, and substrate channeling. Biochemistry 49:3774-3782.
  7. Baker P., Pan, D., Carere, J., Rossi, A., Wang, W. and Seah, S.Y.K. (2009) Characterization of an aldolase/dehydrogenase complex that exhibits substrate channeling in the polychlorinated biphenyls degradation pathway. Biochemistry 48:6551-6558.

Graduate Students

Perrin Baker (Ph.D.)
Jason Carere (Ph.D.)
Chris Langley (M.Sc.)
Scott Mazurkewich (M.Sc.)

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