August Estabrook
Research Abstract
Through my graduate career I have been very interested in enzymes. Most of my work has been focused on elucidating the many functions of M.HhaI, a cytosine C5 DNA methyltransferase, including baseflipping, active site compressions, and now loop motion. To examine enzyme function I have predominantly used enzyme mutagenesis coupled to kinetics but have endeavored into computational studies, bio-informatics, mass spec, CD, anisotropy, crystallography, AFM, and now steady state and stopped-flow fluorescence. My current project is focused on elucidating the role of a specific loop in M.HhaI known to undergo a conformational rearrangement. To accomplish this I have engineered novel tryptophan residues into this loop and have monitored changes in fluorescence with substrate additions. Two future projects I wish to investigate before I complete my Ph.D. career at UCSB include: i) monitoring M.HhaI loop motion with near-cognate DNA substrates to elucidate the full impact of loop motion on DNA specificity and tight binding, and ii) monitor FRET between a fluorescent base analog as it flips and engineered tryptophan residues on the enzyme surface to identifying the groove of DNA which is utilized by the target base as it flips. I suspect my future research will focus on enzymes and their roles in specific biological systems.
Papers
- The Coupling of Tight DNA Binding and Base Flipping, Identification of a Conserved Structural Motif in Base Flipping Enzymes [pdf]
R. August Estabrook, Rebecca Lipson, Ben Hopkins, and Norbert Reich. THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 279, No. 30, Issue of July 23, pp. 31419?31428, 2004. - Gold Nanoparticle Decoration of DNA on Silicon[pdf]
Gary Braun, Katsuhiko Inagaki, R. August Estabrook, D. K. Wood, Eran Levy, A. N. Cleland, Geoffrey F. Strouse, and Norbert O. Reich. Langmuir 2005, 21, 10699-10701. - Statistical coevolution analysis and molecular dynamics: Identification of amino acid pairs essential for catalysis[pdf]
R. August Estabrook, Jia Luo, Matthew M. Purdy, Vyas Sharma, Paul Weakliem, Thomas C. Bruice, and Norbert O. Reich. PNAS 2005 vol. 102 no. 4 994-999. - Photo-activated luminescence of CdSe quantum dot monlayers[pdf]
Steve R. Cordero, Pat J. Carson, R. August Estabrook, Geoffrey F. Strouse, Steve, K. Buratto, , J Phys Chem B., 104, 12137-12142, (2000). - Functional Characterization of Escherichia coli DNA Adenine Methyltransferase, a Novel Target for Antibiotics[pdf]
Neda Mashhoon, Michael Carroll, Cynthia Pruss, Joerg Eberhard, Sawako Ishikawa, R. August Estabrook, and Norbert Reich. THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 279, No. 50, Issue of December 10, pp. 52075?52081, 2004.
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