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) use 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.
Structure-function of actin-modifying proteins (in collaboration with Dr. Michael Rosen, Dept. of Biochemistry); the nature of signalling via PAS domains (in collaboration with Dr. Kevin Gardner, Dept. of Biochemistry); and mechanism of histone demethylation via histone demethylases (in collaboration with Dr. Hongtao Yu, Dept. of Pharmacology).
In addition, personal interests include the structure and mechanism of enzymes and metalloenzymes and deducing previously unknown function from structure.
RESEARCH INTERESTS
Molecular mechanisms of neurotransmitter release, as studied by x-ray crystallography.
Structure and function of lipoproteins from the bacterium T. pallidum, the causative agent of syphilis.
Structure and mechanism of enzymes and metalloenzymes.
Structure of proteins involved in cell signaling and division.
RECENT PUBLICATIONS
Yang M., Culhane J.C., Szewczuk L.M., Gocke C.B., Brautigam C.A., Tomchick D.R., Machius M., Cole P.A., Yu H., "Structural basis of histone demethylation by LSD1 revealed by suicide inactivation." Nat. Struct. Mol. Biol., 14:535-539, 2007
Chosed R., Tomchick D.R., Brautigam C.A., Mukherjee S., Negi V.S., Machius M., Orth K., "Structural analysis of Xanthomonas XopD provides insights into substrate specificity of ULPs." J. Biol. Chem., 282:6773-6782, 2007
Deka R.K., Brautigam C.A., Tomson F.L., Lumpkins S.B., Tomchick D.R., Machius M., Norgard M.V., "Crystal structure of the Tp34 (TP0971) lipoprotein of Treponema pallidum: Implications of its metal-bound state and affinity for human lactoferrin." J. Biol. Chem., 287:5944-5958, 2007
Yang M., Gocke C.B., Luo X., Borek D., Tomchick D.R., Machius M., Otwinowski Z., Yu H., "Structural basis for CoREST-dependent demethylation of nucleosomes by the human LSD1 histone demethylase." Molecular Cell, 23:377-387, 2006
Lu J., Machius M., Dulubova I., Dai H., Sudhof T.C., Tomchick D.R., Rizo J., "Structural basis for a Munc13-1 Homodimer to Munc13-1/RIM heterodimer switch." PLOS Biology, Vol. 4, No. 7:e192 doi:10.1371/journal.pbio.0040192, 2006
SIGNIFICANT PUBLICATIONS
Brannigan J.A., Dodson G., Duggleby H.J., Moody P.C.E., Smith J.L., Tomchick D.R., and Murzin A.G., "A protein catalytic framework with an N-terminal nucleophile is capable of self-activation." Nature, 378:416-419, 1995
Rayment I., Rypniewski W.R., Schmidt-Base K., Smith R., Tomchick D.R., Benning M.M., Winkelmann D.A., Wesenberg G., and Holden H.M., "Three-dimensional structure of myosin subfragment-1: a molecular motor." Science, 261:50-58, 1993
Otomo T., Tomchick D.R., Otomo C., Panchal S.C., Machius M., Rosen M.K., "Structural basis of actin filament nucleation and processive capping by a formin homology 2 domain." Nature, 433:488-494, 2005
Otomo T., Otomo C., Tomchick D.R., Machius M., Rosen M.K., "Structural basis of Rho GTPase-mediation activation of the formin mDia1." Molecular Cell, 18:273-281, 2005
Deka R.K., Brautigam C.A., Yang X.F., Blevins J.S., Machius M., Tomchick D.R., 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., 281:8072-8081, 2006
Point and right click (click and hold for Mac users) your mouse onand select "Save this link (or target) as..." option to save the file to your local computer.
and select "Save this link (or target) as..." option to save the file to your local computer.