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Frank Raushel

Raushel, Frank
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.

Recent Publications

  1. Huddleston, JP, Raushel, FM. Biosynthesis of GDP-d-glycero-α-d-manno-heptose for the Capsular Polysaccharide of Campylobacter jejuni. Biochemistry. 2019;58 (37):3893-3902.
    doi: 10.1021/acs.biochem.9b00548. PubMed PMID:31449400. .

  2. Hogancamp, TN, Cory, SA, Barondeau, DP, Raushel, FM. Structure and Chemical Reaction Mechanism of LigU, an Enzyme That Catalyzes an Allylic Isomerization in the Bacterial Degradation of Lignin. Biochemistry. 2019;58 (33):3494-3503.
    doi: 10.1021/acs.biochem.9b00549. PubMed PMID:31339729. .

  3. Huddleston, JP, Thoden, JB, Dopkins, BJ, Narindoshvili, T, Fose, BJ, Holden, HM et al.. Structural and Functional Characterization of YdjI, an Aldolase of Unknown Specificity in Escherichia coli K12. Biochemistry. 2019;58 (31):3340-3353.
    doi: 10.1021/acs.biochem.9b00326. PubMed PMID:31322866. .

  4. Huddleston, JP, Raushel, FM. Functional Characterization of YdjH, a Sugar Kinase of Unknown Specificity in Escherichia coli K12. Biochemistry. 2019;58 (31):3354-3364.
    doi: 10.1021/acs.biochem.9b00327. PubMed PMID:31314509. .

  5. Xiang, DF, Bigley, AN, Desormeaux, E, Narindoshvili, T, Raushel, FM. Enzyme-Catalyzed Kinetic Resolution of Chiral Precursors to Antiviral Prodrugs. Biochemistry. 2019;58 (29):3204-3211.
    doi: 10.1021/acs.biochem.9b00530. PubMed PMID:31268686. PubMed Central PMC6822272.

  6. Bigley, AN, Raushel, FM. The evolution of phosphotriesterase for decontamination and detoxification of organophosphorus chemical warfare agents. Chem. Biol. Interact. 2019;308 :80-88.
    doi: 10.1016/j.cbi.2019.05.023. PubMed PMID:31100274. PubMed Central PMC6622166.

  7. Taylor, ZW, Raushel, FM. Manganese-Induced Substrate Promiscuity in the Reaction Catalyzed by Phosphoglutamine Cytidylyltransferase from Campylobacter jejuni. Biochemistry. 2019;58 (16):2144-2151.
    doi: 10.1021/acs.biochem.9b00189. PubMed PMID:30929435. PubMed Central PMC6643276.

  8. Bigley, AN, Desormeaux, E, Xiang, DF, Bae, SY, Harvey, SP, Raushel, FM et al.. Overcoming the Challenges of Enzyme Evolution To Adapt Phosphotriesterase for V-Agent Decontamination. Biochemistry. 2019;58 (15):2039-2053.
    doi: 10.1021/acs.biochem.9b00097. PubMed PMID:30893549. .

  9. Mukherjee, K, Huddleston, JP, Narindoshvili, T, Nemmara, VV, Raushel, FM. Functional Characterization of the ycjQRS Gene Cluster from Escherichia coli: A Novel Pathway for the Transformation of d-Gulosides to d-Glucosides. Biochemistry. 2019;58 (10):1388-1399.
    doi: 10.1021/acs.biochem.8b01278. PubMed PMID:30742415. PubMed Central PMC6613369.

  10. Bigley, AN, Xiang, DF, Narindoshvili, T, Burgert, CW, Hengge, AC, Raushel, FM et al.. Transition State Analysis of the Reaction Catalyzed by the Phosphotriesterase from Sphingobium sp. TCM1. Biochemistry. 2019;58 (9):1246-1259.
    doi: 10.1021/acs.biochem.9b00041. PubMed PMID:30730705. PubMed Central PMC6686203.

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