Bio

Current Role at Stanford


Cellular and Molecular Biology PhD Student

Honors & Awards


  • Bio-X Bowes Fellow, Stanford Bio-X (2014)

Professional Affiliations and Activities


  • Career Development Chair, BioAIMs (2014 - Present)

Stanford Advisors


Publications

Journal Articles


  • Role of Metal Ions on the Activity of Mycobacterium tuberculosis Pyrazinamidase AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Sheen, P., Ferrer, P., Gilman, R. H., Christiansen, G., Moreno-Roman, P., Gutierrez, A. H., Sotelo, J., Evangelista, W., Fuentes, P., Rueda, D., Flores, M., Olivera, P., Solis, J., Pesaresi, A., Lamba, D., Zimic, M. 2012; 87 (1): 153-161

    Abstract

    Pyrazinamidase of Mycobacterium tuberculosis catalyzes the conversion of pyrazinamide to the active molecule pyrazinoic acid. Reduction of pyrazinamidase activity results in a level of pyrazinamide resistance. Previous studies have suggested that pyrazinamidase has a metal-binding site and that a divalent metal cofactor is required for activity. To determine the effect of divalent metals on the pyrazinamidase, the recombinant wild-type pyrazinamidase corresponding to the H37Rv pyrazinamide-susceptible reference strain was expressed in Escherichia coli with and without a carboxy terminal. His-tagged pyrazinamidase was inactivated by metal depletion and reactivated by titration with divalent metals. Although Co(2+), Mn(2+), and Zn(2+) restored pyrazinamidase activity, only Co(2+) enhanced the enzymatic activity to levels higher than the wild-type pyrazinamidase. Cu(2+), Fe(2+), Fe(3+), and Mg(2+) did not restore the activity under the conditions tested. Various recombinant mutated pyrazinamidases with appropriate folding but different enzymatic activities showed a differential pattern of recovered activity. X-ray fluorescence and atomic absorbance spectroscopy showed that recombinant wild-type pyrazinamidase expressed in E. coli most likely contained Zn. In conclusion, this study suggests that M. tuberculosis pyrazinamidase is a metalloenzyme that is able to coordinate several ions, but in vivo, it is more likely to coordinate Zn(2+). However, in vitro, the metal-depleted enzyme could be reactivated by several divalent metals with higher efficiency than Zn.

    View details for DOI 10.4269/ajtmh.2012.10-0565

    View details for Web of Science ID 000306153500026

    View details for PubMedID 22764307

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