Biological Chemistry

Paul S. Cremer (Investigation of Lipid Flip-Flop in Solid Supported Membranes) Our laboratory is investigating the transmembrane translocation of phospholipids in biogenic membranes from a surface science perspective. The enzymes responsible for lipid translocation in these membranes, known as flippases, are believed to operate in the absence of an external energy source such as ATP hydrolysis. Further, measured lipid flipping rates show little temperature or head group dependence. One possible mechanism that would explain these observations is the creation of a hydrophilic groove by the enzyme across the bilayer. Such a groove could allow the facile transport of lipids from one leaflet of the bilayer to the other while being only mildly temperature dependent and requiring no external energy source. To test the plausibility of such a mechanism our group will utilize model phospholipid bilayers supported on glass substrates. Models of hydrophilic grooves can be readily engineered into such membranes by a simple modification of the underlying substrate. Once such groove-like features have been incorporated, a variety of spectroscopic techniques then allows the kinetics of lipid flipping to be monitored.

Victoria J. DeRose (Bioinorganic and Biophysical Chemistry) Research in our laboratory addresses the following general question: How do nucleic acids and proteins tune the properties of metal ions to optimize chemical activity? In nucleic acids, we are focussed on the role of metal ions in the chemical reactions catalyzed by RNA, which is a novel biocatalyst. Metals are important for both folding and chemistry in RNA molecules and we are investigating both properties in ribozymes and in RNA structural motifs such as stable tetraloop sequences. In protein-based projects, we are exploring the role of proteins in creating metal-based catalytic centers by investigating small metal-peptide complexes based on protein active sites. The active sites of blue copper proteins and of Fe- and Co-containing nitrile hydratases are current targets. In both projects we rely on spectroscopic methods including EPR, NMR, and the related double-resonance technique of ENDOR, to probe the local structure of metals in biomolecules.

John P. Fackler, Jr. (Gold Drugs) The synthesis and characterization of gold-sulfur compounds have helped develop an understanding of the role of gold(I) medicinals in treatment of rheumatoid arthritis. Our laboratory has pioneered the synthesis and characterization of water soluble gold(I) phosphines. However, few water soluble gold(I) thiols are well characterized. The goal of our research program is to explore the syntheses of new water soluble gold drugs that are less toxic than the currently used materials. In this vain we will look at water soluble gold(I) nitrogen compounds and examine the reactivity of peroxynitrite toward organic compounds in the presence of these gold containing materials.

Paul F. Fitzpatrick (Mechanism of Enzyme Action) Our research is directed at understanding the chemical basis for the tremendous catalytic powers of enzymes. There are two families of enzymes under investigation: metalloenzymes which catalyze the initial steps in the formation of the neurotransmitters serotonin and epinephrine and flavoenzymes which catalyze the oxidation of organic acids in a variety of metabolic pathways. The methods we use range from cloning and site-directed mutagenesis to steady state and rapid reaction kinetics.

Yi-Qin Gao (Theoretical and Computational Biophysics) Biological systems operate under conditions far from equilibrium. Special classes of proteins called motor proteins enable the biological systems to transduce chemical energy into mechanical work. Making use of various theoretical tools, including molecular dynamic and kinetic simulations, we try to understand the molecular detailed mechanisms of these energy transduction processes. We are also trying to understand how a large variety of chemical and mechanical events form a robust and efficient network, which yields biological systems the capability of surviving, reproducing, and responding to the environment.

Paul A. Lindahl (Chemical Mechanism of Minimal Cell Dynamics) Within the next decade, the function of every gene and protein in simple organisms will probably be known. We are examining how these components interact with each other to allow organisms to grow and divide. The student working on this project would collect and organized literature information regarding the metabolism and cell cycle processes for the simplest living organism, Mycoplasma genitalium. This information will be used to develop chemical mechanisms to describe the life of this organism. Students should have some knowledge of cellular biochemistry and have good organizational computer skills.

Robert R. Lucchese We study processes that involve electrons being scattered by or ejected from molecules. These processes include electron-molecule collision, electron impact ionization, and photoionization. Recently we have worked closely with experimental groups around the world to study molecular frame photoelectron angular distributions. In these studies we make detailed comparisons of experimental data and theoretical predictions of the probability of the emission of the photoelectron in specific directions relative to the orientation of the molecule. A second area of interest is the structure and dynamics of hydrogen bonded clusters. This work is done in collaboration with Professor J. W. Bevan's research group who study the corresponding systems experimentally. We develop potential energy surfaces using both experimental data and by performing quantum mechanical electronic structure calculations. The results of this work will give a better understanding of important hydrogen bonded systems including liquid water and many systems of biological interest.

Frank M. Raushel (Mechanistic Enzymology) The primary area of interest for our laboratory is the understanding of the structure, mechanism, and evolution of enzyme active sites. We are engaged in a variety of research projects that are directed at the elucidation of the fundamental factors that contribute to the enormous rate enhancements and exquisite substrate specificity displayed by enzymes. The principal proteins under current investigation include carbamoyl phosphate synthetase, phosphotriesterase, and dihydroorotase. Undergraduate students working in this laboratory will learn how to purify proteins from bacterial sources, construct site-directed and random mutants and characterized these enzymes using a variety of kinetic methods.

Daniel Romo (Synthetic and Mechanistic Studies of Marine Natural Products) A primary interest in our research group is the development of novel and efficient strategies for the total synthesis of bioactive natural products and designed derivatives. These latter compounds will enable investigations into the mechanism of action of these natural products in collaborative efforts with biochemists and biologists. Current natural products being studied in our group include the potent and complex immunosuppressants, pateamine A (PatA) and palau’amine, the potent toxin gymnodimine, and the potential antibiotic, phakellin. As an example, the NSF REU participant may be involved in the design and synthesis of designed derivatives of PatA useful for cellular receptor isolation or for probing PatA–receptor interactions by our collaborator, Prof. Jun Liu (MIT). Thus, a student would be primarily exposed to modern synthetic organic techniques but would also have opportunities to explore molecular modeling and be exposed to concepts in cellular biology.

Eric E. Simanek (Protein Regulation through Glycosylation) We are exploring the mechanisms that cells use to control protein function. While transient phosphorylation is well explored, little attention has been paid to transient glycosylation (addition of a single sugar). We are isolating the enzymes and targets of transient glycosylation, designing substrates and inhibitors to study these events, and develop models to understand the structural consequences of glycosylation.

For more information, write the Graduate Student Advisor: gradmail@mail.chem.tamu.edu.

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