We look at life at the atomic level. To that end, we use high-resolution techniques, primarily X-ray crystallography, but also nuclear magnetic resonance spectroscopy (NMR), to determine the three-dimensional structures of proteins and protein complexes. In addition, we employ a variety of biophysical techniques, combined with the power of mutagenesis studies, to investigate static and dynamic aspects of regulation, enzymatic mechanism, protein-protein interactions, and drug design.
As part of the UTSW core labs, we specialize in collaborating with researchers on campus, thus combining the expertise of our collaborators in their respective fields with our expertise in structural biology. This model allows us to tackle complicated biological problems in a comprehensive way involving many different approaches and techniques.
Current projects include:
Enzymatic and regulatory mechanisms that alpha-ketoacid dehydrogenase multi-enzyme complexes (such as pyruvate dehydrogenase) used to funnel reaction products from glycolysis and amino acid metabolism into the Krebs cycle (collaboration with Dr. David Chuang, Dept. of Biochemistry).
Molecular mechanisms of neurotransmitter release (collaboration with Dr. Josep Rizo, Dept. of Biochemistry). A combination of techniques including X-ray crystallography and NMR is used to study proteins and protein-protein interactions involved in the release of neurotransmitters.
Lipoproteins from the bacterium T. pallidum, the causative agent for syphilis (collaboration with Dr. Michael Norgard, Dept. of Microbiology). Techniques derived from high-throughput structural genomics are used to decipher the function of a class of proteins from an organism that cannot be cultivated in vitro and is therefore not amenable to functional studies using classical biochemical and genetic methods.
Other projects include:
Molecular mechanisms of proteins involved in histone demethylation (collaboration with Dr. Hongtao Yu, Dept. of Pharmacology).
Molecular mechanisms of proteins involved in the spindle checkpoint (collaboration with Dr. Xuelian Luo, Dept. of Pharmacology).
Molecular mechanisms of actin polimerization (collaboration with Dr. Michael Rosen, Dept. of Biochemistry).
Molecular mechanisms of cystic fibrosis transmembrane conductance regulator (CFTR) (collaboration with Dr. Philip Thomas, Dept. of Physiology).
Molecular mechanisms of proteins involved in hypoxia response (collaboration with Dr. Kevin Gardner, Dept. of Biochemistry).
In addition, personal interests include applying biophysical techniques to assess ligand binding and the structural elucidation of enzymatic mechanisms.
RESEARCH INTERESTS
Structural Biology/X-ray Crystallography
Analytical Ultracentrifugation
Isothermal Titration Calorimetry
Structural Elucidation of Enzymatic Mechanisms
Protein-protein interactions
RECENT PUBLICATIONS
Hoopman, T.C., Wang, W., Brautigam, C.A., Reilly, T.J., and Hansen, E.J., "Moraxella catarrhalis synthesizes an autotransporter that is an acid phosphatase." J. Bacteriol., in press, 2007
Huang, N., Sorci, L., Zhang, X., Brautigam, C., Li, X., Raffaelli, N., Magni, G., Grishin, N.V., Osterman, A., & Zhang, H., "Bifunctional NMN adenylyltransferase/ADP ribose pyrophosphatase: structure and function in bacterial NAD metabolism." Structure, in press, 2007
Machius, M., Brautigam, C.A., Tomchick, D.R., Ward, P., Otwinowski, Z., Blevins, J.S., Deka, R.K., and Norgard, M.V., "Structural and biochemical basis for polyamine binding to the Tp0655 lipoprotein of Treponema pallidum: putative role for Tp0655 (TpPotD) as a polyamine receptor." J. Biol. Chem., 373:681-694, 2007
Yang, M., Culhane, J.C., Szewczuk, L.M., Gocke, C.B., Brautigam, C.A., Tomchick, D.R., Machius, M., Cole, P.A., and Yu, H., "Structural basis of histone demethylation by LSD1 revealed by suicide inactivation." Nat. Struct. Molec. Biol., 14:535-539, 2007
Chosed, R., Tomchick, D.R., Brautigam, C.A., Mukherjee, S, Negi, V.S., Machius, M., and Orth, K., "Structural analysis of Xanthomonas XopD provides insights into its substrate specificity." J. Biol. Chem., 282:6773-6782, 2007
SIGNIFICANT PUBLICATIONS
Deka, R.K., Brautigam, C.A., Tomson, F.L., Machius, M., Tomchick, D.R., and Norgard, M.V., "Crystal structure of the Tp34 (TP0971) lipoprotein of Treponema pallidum: biological implications of its metal-bound state and affinity for human lactoferrin." J. Biol. Chem., 282:5944-5958, 2007
Brautigam, C.A., Wynn, R.M., Chuang, J.C., Machius, M., Tomchick, D.R., and Chuang, D.T., "Structural insight into interactions between dihydrolipoamide dehydrogenase (E3) and E3 binding protein of human pyruvate dehydrogenase complex." Structure, 14:611-621, 2006
Deka, R.K., Brautigam, C.A., Yang, X.F., Blevins, J.S., Machius, M., Tomchick, D.R., and Norgard, M.V., "The PnrA (Tp0319; TmpC) lipoprotein represents a new family of bacterial purine nucleoside receptor encoded within an ATP-binding cassette (ABC)-like operon in Treponema pallidum." J. Biol. Chem., 279:55644-55650, 2006
Thibodeau, P.H., Brautigam, C.A., Machius, M., and Thomas, P.J., "Side-chain and backbone contributions of F508 to CFTR folding." Nat. Struct. Molec. Biol., 12:10-16, 2005
Brautigam, C.A., Smith, B.S., Ma, Z., Palnitkar, M., Tomchick, D.R., Machius, M., and Deisenhofer, J., "Crystal structure of the photolyase-like domain of Cryptochome 1 from Arabidopsis thaliana." Proc. Natl. Acad. Sci. (USA), 101:12142-12147, 2004
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