Biochemistry Department - Primary Faculty
Vivien Yee, Ph.D.
- Ph.D.: University of British Columbia, Vancouver, Canada
- Postdoc: Michigan State University, East Lansing, MI
- Postdoc: University of Washington, Seattle, WA
Our structural biology group investigates biomedically important proteins and enzymes with interesting mechanistic questions. Some of our current projects focus on proteins involved in drug metabolism, neurodegenerative disorders, antiviral defense, or are model systems for metabolic enzymes. Our laboratory combines X-ray crystallography with modeling and mutagenesis studies to investigate several systems. One focus is on biotin-dependent enzymes which are important in a variety of metabolic processes. We study the large bacterial transcarboxylase multienzyme complex which is a model for homologous human proteins. Our structures allow us to speculate on catalytic mechanisms and the structural consequences of human disease mutations. We are also investigating the prion protein, whose structural transformation to a pathogenic form is believed to be important in an intriguing family of neurological diseases, the spongiform encephalopathies. By comparing structures of wild-type and mutant prion proteins, our goal is to highlight structural features which may play a role in the disease process. A third project is part of a large pharmacogenomics investigation of drug metabolizing enzymes. Using a combination of experimental and computational methods, we compare wild-type and variant enzyme structures in order to understand the molecular and functional consequences of genetic polymorphisms responsible for variation in patient drug responses.
- Feng Q., Vannaprasaht S., Peng Y., Angsuthum S., Avihingsanon Y., Yee V. C., Tassaneeyakul W., and Weinshilboum R. M.
“Thiopurine S-methyltransferase pharmacogenetics: functional characterization of a novel rapidly degraded variant allozyme”
Biochem Pharmacol 79 (7): 1053-61 (2010). Read article in PubMedCentral
- Lee S., Antony L., Hartmann R., Knaus K. J., Surewicz K., Surewicz W. K., and Yee V. C.
“Conformational diversity in prion protein variants influences intermolecular beta-sheet formation”
EMBO J 29 (1): 251-62 (2010). Read article in PubMedCentral
- Pereira N. L., Aksoy P., Moon I., Peng Y., Redfield M. M., Burnett J. C., Jr., Wieben E. D., Yee V. C., and Weinshilboum R. M.
“Natriuretic peptide pharmacogenetics: membrane metallo-endopeptidase (MME): common gene sequence variation, functional characterization and degradation”
J Mol Cell Cardiol 49 (5): 864-74 (2010).
- Wu T. Y., Peng Y., Pelleymounter L. L., Moon I., Eckloff B. W., Wieben E. D., Yee V. C., and Weinshilboum R. M.
“Pharmacogenetics of the mycophenolic acid targets inosine monophosphate dehydrogenases IMPDH1 and IMPDH2: gene sequence variation and functional genomics”
Br J Pharmacol 161 (7): 1584-98 (2010). Read article in PubMedCentral
- Aksoy P., Zhu M. J., Kalari K. R., Moon I., Pelleymounter L. L., Eckloff B. W., Wieben E. D., Yee V. C., Weinshilboum R. M., and Wang L.
“Cytosolic 5'-nucleotidase III (NT5C3): gene sequence variation and functional genomics”
Pharmacogenet Genomics 19 (8): 567-76 (2009). Read article in PubMedCentral
- Collard F., Zhang J., Nemet I., Qanungo K. R., Monnier V. M., and Yee V. C.
“Crystal structure of the deglycating enzyme fructosamine oxidase (amadoriase II)”
J Biol Chem 283 (40): 27007-16 (2008). Read article in PubMedCentral
- Peng Y., Feng Q., Wilk D., Adjei A. A., Salavaggione O. E., Weinshilboum R. M., and Yee V. C.
“Structural basis of substrate recognition in thiopurine s-methyltransferase”
Biochemistry 47 (23): 6216-25 (2008). Read article in PubMedCentral
- Hall P. R., Zheng R., Antony L., Pusztai-Carey M., Carey P. R., and Yee V. C.
“Transcarboxylase 5S structures: assembly and catalytic mechanism of a multienzyme complex subunit”
EMBO J 23 (18): 3621-31 (2004). Read article in PubMedCentral
- Hall P. R., Zheng R., Pusztai-Carey M., van den Akker F., Carey P. R., and Yee V. C.
“Expression and crystallization of several forms of the Propionibacterium shermanii transcarboxylase 5S subunit”
Acta Crystallogr D Biol Crystallogr 60 (Pt 3): 521-3 (2004).
- Hartmann R., Justesen J., Sarkar S. N., Sen G. C., and Yee V. C.
“Crystal structure of the 2'-specific and double-stranded RNA-activated interferon-induced antiviral protein 2'-5'-oligoadenylate synthetase”
Mol Cell 12 (5): 1173-85 (2003).