Contact Waterloo Institute for Nanotechnology
Mike & Ophelia Lazaridis Quantum-Nano Centre, Room 3606
University of Waterloo
200 University Ave. W.
Waterloo, ON. N2L 3G1
+1 519 888 4567, ext.38654
Research interests: mechanistic enzymology; recombinant DNA and biophysical methods; medicinal chemistry and molecular modeling
Professor John Honek developed novel amino acid analogs used to investigate protein structure/function and control metalloenzyme activity and uniquely applies biological chemistry to areas of nanotechnology such as bioencapsulation and biomaterial interfaces.
The Honek Lab, operating within the University of Waterloo Chemistry department, works at the interface of chemistry and biochemistry. Group members apply chemical and biochemical principles and techniques to the problems of protein structure/function as well as to elucidate the chemical mechanisms of several key enzymes, some of which have medical importance.
Honek received his BSc (Honours Chemistry) from McGill University in 1977, and obtained his PhD (Chemistry) in 1984 also from McGill University under the direction of the late Professor Bernard Belleau, one of the discoverers of the anti-AIDS drug 3TC. Honek took up FCAC (Québec) and Natural Sciences and Engineering Research Council of Canada (NSERC) Postdoctoral Fellowships to continue his studies (1984, 1985) under the direction of Professor Christopher Walsh at Massachusetts Institute of Technology (MIT), U.S.A., where he worked on the biochemistry of biogenic methane production. Honek joined the University of Waterloo Chemistry department in 1986 and held the role of Chemistry Department Chair from 2007 to 2014.
- Postdoctoral Fellow: Massachusetts Institute of Technology
- PhD, Chemistry, McGill University, 1984
- BSc, Chemistry, McGill University, 1977
Awards and Honours
|Year||Awards and Honours|
|2014||Canadian Society for Chemistry (CSC) Bernard Belleau Award, sponsored by Vertex Pharmaceuticals (Canada) Inc.|
Areas of focus
Professor Honek’s interest is to understand the fundamental interactions of small molecules (such as substrates and drugs) with enzymes as well as the mechanisms by which enzymes catalyze reactions. Research in this area includes mechanistic enzymology, recombinant DNA and biophysical methods as well as organic synthesis, medicinal chemistry and molecular modeling. An additional focus is in the area of bionanotechnology and the application of biological chemistry to the synthesis of new nanomaterials and nanostructures.
Biological chemistry of the carbon-sulfur bond
Knowledge of an enzyme’s catalytic mechanism can be of fundamental importance as well as a critical factor in the design and synthesis of inhibitors having therapeutic potential. The group is currently focused on the biological chemistry of the carbon-sulfur bond as it relates to the amino acid methionine and its biochemical function in proteins as well as the study of the enzyme glyoxalase I, a detoxification metalloenzyme that utilizes a sulfur-containing cofactor, glutathione.
Two areas are of current interest. The first is the investigation of extremely large multisubunit proteins which contain internal cavities. These nanosized proteins may be useful as novel drug carriers and as molecular foundations for nanodevices. The second area is the study of the molecular level interactions between biomolecules and nanomaterials. We have utilized phage display methods and unnatural amino acid incorporation techniques to identify peptide sequences that have strong affinity to single-walled carbon nanotubes.
- Bioorganic/biological chemistry
- Medicinal chemistry
- A. A. Petrie, A. M. van der Ven, and J. F. Honek, 2013, Nanomaterial-based Biosensors in Biosensors and Their Applications in Healthcare: Hot Topics, eBook, Future Science Ltd., U.K.
- J. F. Honek, 2013, Aeruginolysin in Handbook of Proteolytic Enzymes 3rd Edition. Rawlings, N. D. and Salvesen, G. Eds., Elsevier Limited, 867-872.
- K. Y. Mullings, N. Sukdeo, U. Suttisansanee, Y. Ran, and J. F. Honek, 2012, Ni2+-Activated Glyoxalase I from Escherichia coli: Substrate Specificity, Kinetic Isotope Effects and Evolution Within the βαβββ Superfamily. Journal of Inorganic Biochemistry, 108, 133-140.
U. Suttisansanee, K. Lau, S. Lagishetty, K. N. Rao, S. Swaminathan, J. M. Sauder, S. K. Burley and J. F. Honek, 2011, Structural Variation in Bacterial Glyoxalase I Enzymes: Investigation of the Metalloenzyme Glyoxalase I from Clostridium acetobutylicum. Journal of Biological Chemistry, 286, 38367-38374.
D. Pradhan, Z. Su, S. Sindhwani, J. Honek and K. T. Leung, 2011, Electrochemical Growth of ZnO Nanobelt-Like Structures at 0 oC: Synthesis, Characterization, and in-situ Glucose Oxidase Embedment.Journal of Physical Chemistry C, 115, 18149-18156.
J. F. Honek, 2012, Aeruginolysin in Handbook of Proteolytic Enzymes 3rd Edition. Rawlings, N. D. and Salvesen, G. Eds., Elsevier Limited, in press.
I. A. Moya, G. D. Westrop, G. H. Coombs and J. F. Honek, 2011, Mechanistic Studies on the Enzymatic Processing of Fluorinated Methionine Analogs by Trichomonas vaginalis Methionine γ-Lyase.Biochemical Journal, 438, 513-521.
Z. Su, S. Zhu, A. Donkor, C. Tzoganakis and J. F. Honek, 2011, Controllable Delivery of Small Molecule Compounds to Targeted Cells Utilizing Carbon Nanotubes. Journal of the American Chemical Society, 133, 6874-6877.
U. Suttisansanee and J. F. Honek, 2011, Bacterial Glyoxalase Enzymes. Seminars in Cell and Developmental Biology, 22, 285-292.
- M. Palmer, J. F. Honek and T. Dieckmann, Introduction to Biochemical Pharmacology, Wiley-VCH (2011), in press.
- C. L. Myers, P. C. Hang, G. Ng, J. Yuen, and J. F. Honek, 2010, Semi-synthetic Analogues of Thiostrepton Delimit the Critical Nature of Tail Region Modifications in the Control of Protein Biosynthesis and Antibacterial Activity. Bioorg. Med. Chem., 18 (12), 4231-4237.
- J. F. Honek, A. Francq, and A. J. Carty, 2010, Research Spotlight: Bionanotechnology: Small Can Have a Big Impact in the Medical Sciences: a WIN-Win Situation. Part 2. Future Medicinal Chemistry 2(11), 1627-1632.
- J. F. Honek, A. Francq, and A. J. Carty, 2010 Research Spotlight: Bionanotechnology: Small Can Have a Big Impact in the Medical Sciences: a WIN-Win Situation. Part 1. Future Medicinal Chemistry 2(10), 1515-1522.
- J. F. Honek, 2009, Biochemistry of the Ni(II)-dependent Glyoxalase I Enzymes. J. Biol. Inorg. Chem. 14 (suppl 1): S73.
- A. Moya, Z. Su and J. F. Honek, 2009, Current and Future Perspectives on the Chemotherapy of the Parasitic Protozoa Trichomonas vaginalis and Entamoeba histolytica. Future Medicinal Chemistry 1(4), 619-643.
- Z. Su, K. Mui, E. Daub, T. Leung, and J. F. Honek, 2009, Interactions of Peptides with Single-Walled Carbon Nanotubes. Adv. Exp. Med. Biol. 611, 235-236.
- M. S. Dunstan, P. C. Hang, N. V. Zelinskaya, J. F. Honek & G. L. Conn, 2009, Structure of the Thiostrepton-Resistance Methyltransferase-S-Adenosyl-L-methionine Complex and Its Interaction with Ribosomal RNA. Jour. Biol. Chem., 284, 17013-17020.
- J. F. Honek, 2009, Effects of Fluorination on the Bioorganic Properties of Methionine in Fluorine in Medicinal Chemistry and Chemical Biology. Ojima, I. and Taguchi, T. Eds., Blackwell-Wiley Publishing.
- Z. Su, N. Sukdeo and J. F. Honek, 2008, 15N-1H HSQC NMR Evidence for Distinct Specificity of Two Active Sites in Escherichia coli Glyoxalase I. Biochemistry, 47, 13232-13241.
- N. Sukdeo and J. F. Honek, 2008, Microbial Glyoxalase Enzymes: Metalloenzymes Controlling Cellular Levels of Methylglyoxal. Drug Metabolism and Drug Interactions, 23, 29-50.
- Z. Su, K. Mui, E. Daub, T. Leung and J. F. Honek, 2007, Single-walled Carbon Nanotube Binding Peptides: Probing Tryptophan’s Importance by Unnatural Amino Acid Substitution. J. Phys. Chem. B, 111, 14411-14417.
- N. Sukdeo and J. F. Honek, 2007, Pseudomonas aeruginosa Contains Multiple Glyoxalase I-Encoding Genes from Both Metal Activation Classes. Biochimica et Biophysica Acta-Proteins and Proteomics, 1774, 756-763.
- Z. Su and J. F. Honek, 2007, Emerging Bacterial Enzyme Targets. Current Opinion in Investigational Drugs, 8, 140-149.
- J. O’Young, N. Sukdeo and J. F. Honek, 2007, Escherichia coli Glyoxalase II is a Binuclear Zinc-Dependent Metalloenzyme. Archives of Biochemistry and Biophysics, 459, 20-26.
- N. Sukdeo, E. Daub and J. F. Honek, 2007, Biochemistry of the Nickel-Dependent Glyoxalase I Enzymes in Metal Ions in Life Sciences, Volume 2 (Wiley), 445-472.
- M. D. Vaughan, V. J. Robertson and J. F. Honek, 2007, Experimental and theoretical studies on inversion dynamics of dichloro(L-difluoromethionine -N,S)platinum(II) and dichloro(L-trifluoromethionine-N,S)platinum(II) complexes. J. Fluorine Chem., 128, 65-70.
- C. E. Hand and J. F. Honek, 2007, Phosphate Transfer from Inositol Pyrophosphates InsP5PP and InsP4(PP)2: A Semi-empirical Investigation. Bioorg. Med. Chem. Lett., 17, 183-188.
- J. F. Honek, Chapter 24, “Fluorinated Methionines as Probes in Biological Chemistry” in “Current Fluoroorganic Chemistry. New Synthetic Directions, Technologies, Materials and Biological Applications” ACS Symposium Series; Soloshonok, V. A.; Mikami, K.; Yamazaki, T.; Welch, J. T., and Honek, J. Eds., Oxford University Press, (2007) p393-408.
- D. K. Garner, M. D. Vaughan, H. J. Hwang, M. G. Savelieff, S. M. Berry, J. F. Honek, and Y. Lu, 2006, Reduction Potential Tuning of the Blue Copper Center in Pseudomonas aeruginosa Azurin by the Axial Methionine as Probed by Unnatural Amino Acids. Jour. Amer. Chem. Soc., 128, 15608-15617.
- Z. Su, T. Leung and J. F. Honek, 2006, Conformational Selectivity of Peptides for Single-Walled Carbon Nanotubes. J. Phys. Chem. B, 110, 23623-23627.
- C. E. Hand, F.-I. Auzanneau and J. F. Honek, 2006, Conformational Analyses of Mycothiol, a Critical Intracellular Glycothiol in Mycobacteria. Carbohydrate Research, 341, 1164-1173.
- P. Walasek and J. F. Honek, 2005, Nonnatural Amino Acid Incorporation into the Methionine 214 Position of the Metzincin Pseudomonas aeruginosa Alkaline Protease. BMC Biochemistry, 6: 21. (Open Access)
- M. D. Vaughan, P. B. Sampson. E. Daub and J. F. Honek, 2005, Investigation of Bioisosteric Effects on the Interaction of Substrates/Inhibitors with the Methionyl-tRNA Synthetase from Escherichia coli. Medicinal Chemistry, 1, 227-237.
- C. E. Hand and J. F. Honek, 2005, Biological Chemistry of Naturally Occurring Intracellular Thiols of Microbial and Marine Origin. Journal of Natural Products, 68, 293-308.
- P. C. Hang and J. F. Honek, 2005, Electronic Structure Calculations on the Thiazole-Containing Antibiotic Thiostrepton: Molecular Mechanics, Semi-Empirical and Ab initio Analyses. Bioorganic and Medicinal Chemistry Letters, 15, 1471-1474.
- C. E. Hand, N. J. Taylor and J. F. Honek, 2005, Ab Initio Studies of the Properties of Intracellular Thiols Ergothioneine and Ovothiol. Bioorganic and Medicinal Chemistry Letters, 15, 1357-1360.
- N. Sukdeo, S. L. Clugston, E. Daub and J. F. Honek, 2004, Distinct Classes of Glyoxalase I. Metal Specificity of the Yersinia pestis, Pseudomonas aeruginosa and Neisseria meningitidis Enzymes. Biochemical Journal, 384, 111-117.
- S. L. Clugston, R. Yajima and J. F. Honek, 2004, Investigation of Metal Binding and Activation of E. coli Glyoxalase I: Kinetic, Thermodynamic and Mutagenesis Studies. Biochemical Journal, 377, 309-316.
- S. L. Jacques, A. Mizra, L. Ejim, K. Koteva, D. W. Hughes, K. Green, R. Kinach, J. F. Honek, H. K. Lai, A. M. Berghuis and G. D. Wright, 2003 , Enzyme Assisted Suicide: Inhibitor Generation in the Active Site of Homoserine Dehydrogenase Accounts for the Antifungal Activity of 5-Hydroxy-4-Oxonorvaline. Chemistry and Biology, 10, 989-995.
- B. Salopek-Sondi, M. D. Vaughan, M. C. Skeels, J. F. Honek and L. A. Luck, 2003, 19F NMR Studies of the Leucine-Isoleucine-Valine Binding Protein: Evidence That a Closed Conformation Exists in Solution. Journal of Biomolecular Structure and Dynamics, 21(2) 235-246..
- T. Crepin, E. Schmitt, Y. Mechulam, P. B. Sampson, M. D. Vaughan, J. F. Honek and S. Blanquet, 2003, Use of Analogues of Methionine and Methionine Adenylate to Sample Conformational Changes During Catalysis in Escherichia coli Methionyl-tRNA Synthetase. Jour. Mol. Biol., 332, 59-72.
- J. A. Steere and J. F. Honek, 2003, Synthesis and Biological Activity of Novel S-Adenosyl-L-Homocysteine Hydrolase Inhibitors. Bioorg. Med. Chem., 11, 3229-3236.
- M. D. Vaughan, P. B. Sampson and J. F. Honek, 2002 , Methionine In and Out of Proteins: Targets for Drug Design. Current Medicinal Chemistry , 9, 385-409.
- J. A. Steere, P. B. Sampson and J. F. Honek, 2002, Synthesis of an alpha-Aminophosphonate Nucleoside as an Inhibitor of S-Adenosyl-L-Homocysteine Hydrolase. Bioorg. Med. Chem. Lett., 12, 457-460.
- H. S. Duewel, E. Daub, V. Robinson and J. F. Honek, 2001 , Elucidation of Solvent Exposure, Side-Chain Reactivity and Steric Demands of the Trifluoromethionine Residue in a Recombinant Protein. Biochemistry , 40, 13167-13176.
- K.-W. Leung, H. S. Duewel, J. F. Honek and A. M. Berghuis, 2001 , Crystal Structure of the Lytic Transglycosylase from Bacteriophage Lambda in Complex with Hexa-N-Acetylchitohexaose. Biochemistry , 40, 5665-5673.
- G. Davidson, S. L. Clugston, J. F. Honek, and M. J. Maroney, 2001 , An XAS Investigation of Product and Inhibitor Complexes of Ni-containing GlxI from E. coli: Mechanistic Implications. Biochemistry , 40, 4569-4582.
- S. L. Jacques, C. Nieman, D. Bareich, G. Broadhead, R. Kinach, J. F. Honek and G. D. Wright, 2001, Characterization of Yeast Homoserine Dehydrogenase, an Antifungal Target: The Invariant Histidine 309 is Important for Enzyme Integrity. Biochim. Biophys. Acta, 1544, 28-41.
- E. Stokvis, S. L. Clugston, J. F. Honek, and A. J. R. Heck, 2000 , Characterization of Glyoxalase I (E. coli)-Inhibitor Interactions by Electrospray Time-of-Flight Mass Spectrometry and Enzyme Kinetics. Jour. Prot. Chem., 19, 389-397.
- M. M. He, S. L. Clugston, J. F. Honek, and B. W. Matthews, 2000 , Determination of the Structure of Escherichia coli Glyoxalase I Suggests a Structural Basis for Differential Metal Activation. Biochemistry , 39, 8719-8727.
- G. Davidson, S. L. Clugston, J. F. Honek, and M. J. Maroney, 2000 , XAS Investigation of the Nickel Active Site Structure in Escherichia coli Glyoxalase I. Inorg. Chem. (ACS), 39 , 2962-2963..
- W. T. Lowther, N. Brot, H. Weissbach, J. F. Honek, and B. W. Matthews, 2000, Thiol-Disulfide Exchange is Involved in the Catalytic Mechanism of Peptide Methionine Sulfoxide Reductase. Proc. Natl. Acad. Sci (USA), 97, 6463-6468.
- S. L. Clugston and J. F. Honek, 2000, Identification of Sequences Encoding the Detoxification Metalloisomerase Glyoxalase I in Microbial Genomes from Several Pathogenic Organisms. Journal of Molecular Evolution , 50, 491-495.
- M. D. Vaughan, P. Cleve, V. Robinson, H. S. Duewel, and J. F. Honek, 1999, Difluoromethionine as a Novel 19F NMR Structural Probe for Internal Amino Acid Packing in Proteins. Jour. Amer. Chem. Soc., 121, 8475-8478.
- W. T. Lowther, Y. Zhang, P. B. Sampson, J. F. Honek, and B. W. Matthews, 1999, Insights into the Mechanism of Escherichia coli Methionine Aminopeptidase from the Structural Analysis of Reaction Products and Phosphorus-Based Transition-State Analogues. Biochemistry, 38, 14810-14819.
- P. B. Sampson and J. F. Honek, 1999, Oxidative Deprotection of Diphenylmethylamines. Organic Letters (ACS), 1, 1395-1397.
- S.L. Clugston, J.F.J. Barnard, R. Kinach, D. Miedema, R. Ruman, E. Daub and J.F. Honek, 1998, Overproduction and Characterization of a Dimeric Non-Zinc Glyoxalase I from Escherichia coli: Evidence for Optimal Activation by Nickel Ions. Biochemistry, 37, 8754-8763.
- H.D. Ly, S.L. Clugston, P.B. Sampson, and J.F. Honek, 1998, Syntheses and Kinetic Evaluation of Hydroxamate-Based Peptide Inhibitors of Glyoxalase I. Bioorganic and Medicinal Chemistry Letters, 8, 705-710.
- S.L. Clugston, E. Daub, and J.F. Honek, 1998, Identification of Glyoxalase I Sequences in Brassica oleracea and Sporobolus stapfianus: Evidence for Gene Duplication Events, Journal of Molecular Evolution, 47, 230-234.
- H.S. Duewel and J.F. Honek 1998, CNBr/Formic Acid Reactions of Methionine- and Trifluoromethionine- Containing Lambda Lysozyme: Probing Chemical and Positional Reactivity and Formylation Side Reactions by Mass Spectrometry, Journal of Protein Chemistry 17, 337-350.
- M.E. Houston Jr., L. Harvath, and J.F. Honek 1997, Syntheses of and Chemotactic Responses Elicited by fMet-Leu-Phe Analogs Containing Difluoro-and Trifluoromethionine. Bioorganic and Medicinal Chemistry Letters, 7, 3007-3012.
- H. Duewel, E. Daub, V. Robinson and J.F. Honek 1997 Incorporation of Trifluoromethionine into a Phage Lysozyme: Implications and a New Marker for Use in Protein 19F NMR. Biochemistry 36, 3404-3416.
- S.L. Clugston, E. Daub, R. Kinach, D. Miedema, J.F.J. Barnard and J.F. Honek 1997. Isolation and Sequencing of a Gene Coding for Glyoxalase I Activity from Salmonella typhimurium and Comparison with Other Glyoxalase I Sequences. Gene 186,103-111.
- P.C. M. Chan, R.J. Roon, J.F. Koerner, N.J. Taylor and J.F. Honek 1995 A 3-Amino-4-Hydroxy-3-Cyclobutene- 1,2-Dione Containing Glutamate Analogue Exhibiting High Affinity to Excitatory Amino Acid Receptors. Journal of Medicinal Chemistry 38, 4433-4438.
- M. Diaz-Diaz, O.P. Ward, J. Honek and G. Lajoie 1995 Enzymes from Pseudomonas sp. NCIB 11097 Participating in Biotransformation of Acetaldehyde and Glycine to Threonine Isomers. Canadian Journal of Microbiology 41, 438-443.
- H. S. Duewel, E. Daub and J. F. Honek 1995 Investigations of the Interactions of Saccharides with the Lysozyme from Bacteriophage Lambda Biochimica et Biophysica Acta 1247,149-158.