Simon Fraser University
Vocadlo
pic of vocadlo

David Vocadlo

Associate Professor and Canada Research Chair in Chemical Biology

Ph.D. - University of British Columbia
Postdoctoral Fellow - University of California, Berkeley

Room C8080
778-782-3530 (office)
778-782-3765 (fax)

dvocadlo@sfu.ca

Chemical Biology

- glycobiology, carbohydrate chemistry, proteomics, post-translational modifications, enzyme inhibitors, mass spectrometry, enzymology


Our group is studying the dynamic post-translational glycosylation of nuclear and cytoplasmic proteins. Nuclear and cytoplasmic glycosylation plays a role in sensing metabolic flux within cells and has been implicated in diabetes mellitus and neurodegenerative disease. We aim to develop new chemical and proteomics tools for studying the role of intracellular glycosylation in cells and tissues as well as the enzymes involved in these processes.


    Representative Publications

  1. R. J. Dennis, E.J. Taylor, M. S. Maculey, K. A. Stubbs, J.P. Turkenburg, S.J. Hart, G. Black, D. J. Vocadlo*, G.J. Davies*. Structure and mechanism of a bacterial b-glucosaminidase having O-GlcNAcase activity. Nat. Struct. Mol. Biol. 2006, In the Press.
  2. N. Cetinbas, M. S. Macauley, K. A. Stubbs, R. Drapala, D. J. Vocadlo* Identification of Asp(174) and Asp(175) as the Key Catalytic Residues of Human O-GlcNAcase by Functional Analysis of Site-Directed Mutants. Biochemistry2006, 45, 3835-3844
  3. K. A. Stubbs, N. Zhang, and D. J. Vocadlo*, A Divergent Synthesis of 2-Acyl Derivatives of PUGNAc Yields Selective Inhibitors of O-GlcNAcase.Org. Biomol. Chem., 2005, 4, 839-845.
  4. K. A. Stubbs, M. A. Macauley, and Vocadlo, D. J. *, A Simple and Concise Synthesis of Aryl 2-acetamido-2-deoxy-1-thio-b-D-glucopyranosides. Carbohydr. Res., 2006, Feb 9, On-Line.
  5. Molecular basis for G protein control of ATP sulfurylase in bacteria. G. J. Mougous, D. H. Lee, S. C. Hubbard, M. W. Schelle, D. J. Vocadlo, J. M. Berger*, and C. R. Bertozzi*. Mol. Cell., 2006, 21, 109-122.
  6. Human O-GlcNAcase catalyses hydrolysis of thioglycosides without acid catalysis. M. S. Macauley, K.A. Stubbs, D. J. Vocadlo*. J. Am. Chem. Soc., 2005, 14, 17202-17203.
  7. M. S. Macauley, G. E. Whitworth, A. Debowski, D. Chin, and D. J. Vocadlo*. Human O-GlcNAcase uses substrate-assisted catalysis: kinetic analysis and development of highly selective, cell permeable, mechanism-inspired inhibitors. J. Biol. Chem.,2005, 280, 25313-25322.
  8. D. J. Vocadlo and S. G. Withers*. Detailed comparative analysis of the catalytic mechanisms of b-N-acetylglucosaminidases from families 3 and 20 of glycoside hydrolases. Biochemistry, 2005, 44, 12809-12818.
  9. D. J. Vocadlo and S. G. Withers*. The chemical synthesis of dissacharide probes of the hen egg white mechanism. Carbohydr. Res.2005,340, 379-88.
  10. D. J. Vocadlo* and C. R. Bertozzi*. A strategy for functional proteomic analysis of glycosidase activity from cell lysates, Angew. Chem. Int. Ed., 2004, 43, 5338-5342.
  11. J. K. Yang, H.-J. Yoon, H. J. Ahn, B. I. Lee, J.-D. Pedelacq, E. C. Liong, J. Berendzen, M. Laivenieks, C. Vieille, G. J. Zeikus, D. J. Vocadlo, S. G. Withers, and S. W. Suh.* Crystal structure of b-d-xylosidase from Thermoanaerobacterium saccharolyticum, a glycoside hydrolase of family 39. J. Mol. Biol.2004, 335, 155-165.
  12. D. J. Vocadlo, H. Hang, E.-J. Kim, J. Hanover, C. R. Bertozzi*. A chemical approach for identification of O-GlcNAc modified proteins. Proc. Nat. Acad. Sci., USA, 2003, 100, 9116-9121.
  13. S. J. Williams, B. L. Mark, D. J. Vocadlo, M.N.G. James, and S. G. Withers*. Aspartate 313 in the Streptomyces plicatus b-hexosaminidase plays a critical role in substrate assisted catalysis by orienting the 2-acetamido group and stabilizing the transition state. J. Biol. Chem., 2002, 277, 40055-40065.
  14. D. J. Vocadlo, J. Wicki, K. Rupitz, S. G. Withers*. A case for reverse protonation: identification of the acid/base catalyst residue in Thermoanaerobacteriumsaccharolyticum -xylosidase and detailed kinetic analysis of a site-directed mutant. Biochemistry2002, 41, 9236-9246.
  15. D. J. Vocadlo, J. Wicki, K. Rupitz, S. G. Withers*. Mechanism of Thermoanaerobacterium saccharolyticum -xylosidase: kinetic studies. Biochemistry2002, 41, 9727-9735.
  16. B. L. Mark, D. J. Vocadlo, S. Knapp, S. G. Withers, M. N. G. James*. Biochemical and structural assessment of the 1-N-azasugar GalNAc-isofagomine as a potent family 20 b-N-acetylhexosaminidase inhibitor. J. Biol. Chem. 2001, 276, 42131-42137.
  17. D. J. Vocadlo, G. J. Davies, R. Laine, S. G. Withers*. Catalysis by hen egg white lysozyme proceeds via a covalent intermediate. Nature. 2001, 412, 835-3838.
  18. B. L. Mark, D. J. Vocadlo, S. Knapp, B. Triggs-Raine, S. G. Withers, M. N. G. James*. Crystallographic evidence for substrate-assisted catalysis in a bacterial b-hexosaminidase. J. Biol. Chem. 2001, 276, 10330-10337.
  19. Y. Hou, D. J. Vocadlo, S. G. Withers, D. Mahuran*. Characterization of the Glu and Asp residues in the active site of human b-hexosaminidase B. Biochemistry. 2001, 40, 2201-2209.
  20. Y. Hou, D. Vocadlo, S. Withers, and D. Mahuran*. Role of Arg211 in the Active Site of Human b-Hexosaminidase B. Biochemistry.2000,39, 6219-6227.
  21. D. J. Vocadlo, C. Mayer, He, S. M., Withers, S. G*. Mechanism of action and identification of Asp242 as the catalytic nucleophile of Vibrio furnisii N-acetyl-b-D-glucosaminidase using 2-acetamido-2-deoxy-5-fluoro-a-L-idopyranosyl fluoride. Biochemistry2000,39, 117-126.