- Frank Raushel
- Professor of Chemistry and of Biochemistry and Biophysics
- ILSB Room 1214A
- Undergraduate Education
- B.A. St. Thomas College (1972)
- Graduate Education
- Ph.D. University of Wisconsin, Madison (1976)
- Postdoc. The Pennsylvania State University (1976-80)
- Joined Texas A&M in 1980
Mechanism and Evolution of Enzyme Active Sites
Enzymes catalyze a remarkable variety of chemical reactions with extremely high rate enhancements and very selective specificities. Our research is directed toward understanding enzyme-catalyzed chemistry and protein structure. Acquiring this information shall provide the framework for the redesign of these complex molecules in an effort to exploit the properties of enzyme active sites for a variety of chemical and medicinal uses. The techniques we use include steady-state and stopped-flow kinetics, NMR spectroscopy, x-ray crystallography, synthesis of inhibitors and suicide substrates, and site-directed mutagenesis to construct new proteins with altered properties. We are applying these methods to the reactions catalyzed by carbamoyl phosphate synthetase, phospho-triesterase, ribonuclease T1and kanamycin nucleotidyl transferase. Phosphotriesterase catalyzes the detoxification of organophosphate insecticides. We recently discovered that the active site consists of a unique binuclear metal center and are now investigating the structure and properties of this metal center as a tool for the evolution of enzyme structure and function. Carbamoyl phosphate synthetase catalyzes the formation of the key precursor for the biosynthesis of arginine and pyrimidine nucleotide. This complex heterodimeric protein contains unique binding sites for 10 substrates, allosteric ligands and metal ion activators.
Raushel, FM. The Discovery of a β-Lactone Synthetase. Biochemistry. 2017;56 (9):1175-1176.
Mabanglo, MF, Xiang, DF, Bigley, AN, Raushel, FM. Correction to Structure of a Novel Phosphotriesterase from Sphingobium sp. TCM1: A Familiar Binuclear Metal Center Embedded in a Seven-Bladed β-Propeller Protein Fold. Biochemistry. 2016;55 (34):4871.
Mabanglo, MF, Xiang, DF, Bigley, AN, Raushel, FM. Structure of a Novel Phosphotriesterase from Sphingobium sp. TCM1: A Familiar Binuclear Metal Center Embedded in a Seven-Bladed β-Propeller Protein Fold. Biochemistry. 2016;55 (28):3963-74.
Bigley, AN, Xiang, DF, Ren, Z, Xue, H, Hull, KG, Romo, D et al.. Chemical Mechanism of the Phosphotriesterase from Sphingobium sp. Strain TCM1, an Enzyme Capable of Hydrolyzing Organophosphate Flame Retardants. J. Am. Chem. Soc. 2016;138 (9):2921-4.
Yang, K, Ren, Z, Raushel, FM, Zhang, J. Structures of the Carbon-Phosphorus Lyase Complex Reveal the Binding Mode of the NBD-like PhnK. Structure. 2016;24 (1):37-42.
Vladimirova, A, Patskovsky, Y, Fedorov, AA, Bonanno, JB, Fedorov, EV, Toro, R et al.. Substrate Distortion and the Catalytic Reaction Mechanism of 5-Carboxyvanillate Decarboxylase. J. Am. Chem. Soc. 2016;138 (3):826-36.
Xiang, DF, Bigley, AN, Ren, Z, Xue, H, Hull, KG, Romo, D et al.. Interrogation of the Substrate Profile and Catalytic Properties of the Phosphotriesterase from Sphingobium sp. Strain TCM1: An Enzyme Capable of Hydrolyzing Organophosphate Flame Retardants and Plasticizers. Biochemistry. 2015;54 (51):7539-49.
Bigley, AN, Mabanglo, MF, Harvey, SP, Raushel, FM. Variants of Phosphotriesterase for the Enhanced Detoxification of the Chemical Warfare Agent VR. Biochemistry. 2015;54 (35):5502-12.
Ren, Z, Ranganathan, S, Zinnel, NF, Russell, WK, Russell, DH, Raushel, FM et al.. Subunit Interactions within the Carbon-Phosphorus Lyase Complex from Escherichia coli. Biochemistry. 2015;54 (21):3400-11.
Xiang, DF, Patskovsky, Y, Nemmara, VV, Toro, R, Almo, SC, Raushel, FM et al.. Function discovery and structural characterization of a methylphosphonate esterase. Biochemistry. 2015;54 (18):2919-30.