I research the determination of protein molecular structure using X-ray diffraction and correlation with function.
Research Information
Research Interests
Dr. Yee's research interests span a variety of biomedically important proteins and enzymes with interesting mechanistic questions. Her lab has studied proteins involved in drug metabolism, neurodegenerative disorders, and antiviral defense, or are model systems for human metabolic enzymes. Her approach combines X-ray crystallography with modeling and mutagenesis studies to investigate the relationship between structure and function in several systems.
Dr. Yee's group published the first crystal structure of the human prion protein, whose conformational 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, her group highlights structural features which may play a role in the disease process. Dr. Yee's lab was also part of a large pharmacogenomics investigation of drug metabolizing enzymes. Using a combination of experimental and computational methods, her group compared 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. Other projects in Dr. Yee's group focused on blood coagulation proteins and on biotin-dependent enzymes which are important in a variety of metabolic processes. Her lab's elucidation of these structures provided insight into catalytic mechanisms and the structural consequences of human disease mutations.
As the Department's Vice Chair for Education, Dr. Yee is responsible for improving program curricula, and developing mentoring and outreach programs.
Publications
- 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).
- 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).
- 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).
- 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).
- 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).
- 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).
- 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).
- 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).