David A. Horita
Assistant Professor of Biochemistry
B.A. (Chemistry), Carleton College, 1988
Ph.D. (Physical Chemistry), University of Wisconsin-Madison, 1994 (L.E. Lerner)
Postdoctoral (NMR Spectroscopy), National Cancer Institute-Frederick (R.A. Byrd)
Phone: (336) 713-4194
E-mail: dhorita@wfubmc.edu
Research in my laboratory focuses on the structural biology underlying regulation of the generation of reactive oxygen species (ROS). ROS generated by the NADPH oxidase enzyme complex are used by macrophages and neutrophils to destroy pathogens and by other cell types as signaling molecules. Excess or unwanted production of ROS can lead to inflammation, and ROS can serve as a trigger for cell death. However, ROS also functions in cell-signaling roles. Hence, proper regulation of ROS production is critical.
We are using solution-state NMR spectroscopy to investigate the interaction between the peripheral membrane proteins of the NADPH oxidase and their cognate lipids. Our model system involves protein domains from the cytosolic components of NADPH oxidase and small membrane mimetics. Understanding of lipid-mediated oxidase activity is of biomedical significance not only in regards to proper immune function (i.e., response to pathogens) but also in regards to improper immune response (i.e., various inflammatory diseases).
Recent Publications
Hantgan, R.R., Stahle, M.C., Connor, J.H., Horita, D.A., Rocco, M., McClane, M.A., Yakovlev, S., & Medved, L. (2006), Integrin alphaIIbbeta3:ligand interactions are linked to binding-site remodeling. Prot. Sci., 15:1893-1906.
Gaponenko, V., Sarma, S.P., Altieri, A.S., Horita, D.A., Li, J. and Byrd, R.A. (2004), Improving the accuracy of NMR structures of large proteins using pseudocontact shifts as long-range restraints. J. Biomol. NMR, 28:205-213.
Hantgan, R.R., Stahle, M.C., Connor, J.H., Lyles, D.S., Horita, D.A., Rocco, M., Nagaswami, C., Weisel, J.W. and McLane, M.A. (2004), The disintegrin echistatin stabilized integrin alphaIIb-beta3's open conformation and promotes its oligomerization. J. Mol. Biol., 342:1625-1636.
Zhou, M., Horita, D.A., Waugh, D.S., Byrd, R.A. and Morrison, D.K. (2002), Solution structure and functional analysis of the cysteine-rich C1 domain of kinase suppressor of Ras (KSR). J. Mol. Biol., 315:435-446.
Horita, D.A., Ivanova, A.V., Altieri, A.S., Klar, A.J.S. and Byrd, R.A. (2001), Solution structure, domain features, and structural implications of mutants of the chromo domain from the fission yeast histone methyltransferase Clr4. J. Mol. Biol., 307:861-870.
Horita, D.A., Zhang, W., Smithgall, T.E., Gmeiner, W.H. and Byrd, R.A. (2000), Dynamics of the Hck SH3 domain: Comparison of Experiment with Multiple Molecular Dynamics Simulations. Protein Sci. 9:95-103.