Our laboratory uses x-ray crystallography as a central tool for studying protein structure and mechanism. Historically, crystallography has been a powerful technique for determining protein folds. Now, with the advances in molecular biology, synchrotron radiation, phasing techniques, and computing, crystallography enables researchers to go beyond a single picture of one enzyme from one organism: it is now possible to elucidate structures of entire enzyme pathways and to capture multiple "snapshots" of enzymes as they proceed through their reaction cycles. Our laboratory combines molecular biology, biochemistry, and spectroscopy with state-of-the-art crystallographic techniques to investigate protein function.
Our research focuses on metalloproteins, since the combination of metals with amino acids allows for the unique reactivity that is essential for all living things. The most fundamental of cellular reactions involve metalloproteins, such as carbon fixation, nucleotide biosynthesis, and photosynthesis. Metalloproteins are also vital for the biosynthesis of natural products, catalyzing some of the more complicated steps in biosynthetic pathways. Below are descriptions of selected projects representative of the types of systems we study, the kinds of information we obtain, and our future directions.
Ryan KS and Drennan CL. (2009) Divergent Pathways in the Biosynthesis of Bisindole Natural Products. Chem. Biol. 16:351-364.
Wong C, Fujimori DG, Walsh CT, Drennan CL. (2009) Structural Analysis of an Open Active Site Conformation of Nonheme Iron Halogenase CytC3. J. Am. Chem. Soc. 191:4972-4979.
Blasiak, LC and Drennan CL. (2009) Structural Perspective on Enzymatic Halogenation. Acc. Chem. Res. 42(1):147-155.
Ryan KS, Chakraborty S, Howard-Jones AR, Walsh CT, Ballou DP, Drennan CL. (2008) The FAD Cofactor of RebC Shifts to an IN Conformation upon Flavin Reduction. Biochemistry. 47:14506-13513.
Vey JL, Yang J, Li M, Broderick WE, Broderick JB, Drennan CL. (2008) Structural Basis for glycyl radical formation by pyruvate formate-lyase activating enzyme. Proc. Natl. Acad. Sci. U.S.A. 105(42):16137-16141.
Phillips CM and Drennan CL. (2008) Nickel regulatory transcription factor, NikR. Handbook of Metalloproteins.
Blasiak LC and Drennan CL. (2008) Nonheme iron halogenases. Handbook of Metalloproteins.
Hernandez HH, Jaquez OA, Hamill MJ, Elliott SJ, Drennan CL. (2008) Thioredoxin Reductase from Thermoplasma acidophilum: A New Twist on Redox Regulation. Biochemistry. 47(37):9728-9737.
Hamill MJ, Chobot SE, Hernandez HH, Drennan CL, Elliott SJ. (2008) Direct Electrochemical Analyses of a Thermophilic Thioredoxin Reductase: Interplay between Conformational Change and Redox Chemistry. Biochemistry. 47(37):9738-9746.
Ryan KS, Balibar CJ, Turo KE, Walsh CT, Drennan CL. (2008) The Violacein Biosynthetic Enzyme VioE Shares a Fold with Lipoprotein Transporter Proteins. J. Biol. Chem. 283(10):6467-6475.
Doukov TI, Blasiak LC, Seravalli J, Ragsdale SW, Drennan CL. (2008) Xenon in and at the End of the Tunnel of Bifunctional Carbon Monoxide Dehydrogenase/Acetyl-CoA Synthase. Biochemistry. 47(11):3474-3483.
Phillips CM, Schreiter ER, Guo Y, Wang SC, Zamble DB, Drennan CL. (2008) Structural Basis of the Metal Specificity for Nickel Regulatory Protein NikR. Biochemistry. 47(7):1938-1946.
Hubbard PA, Padovani D, Labunska T, Mahlstedt SA, Banerjee R, Drennan CL. (2007) Crystal Structure and Mutagenesis of the Metallochaperone MeaB. J. Biol. Chem. 282(43):31308-31316.
Ryan KS, Howard-Jones AR, Hamill MJ, Elliott SJ, Walsh CT, Drennan CL. (2007) Crystallographic trapping in the rebeccamycin biosynthetic enzyme RebC. Proc. Natl. Acad. Sci. U.S.A. 104(39):15311-15316.
Schreiter ER and Drennan CL. (2007) Ribbon-helix-helix transcription factors: variations on a theme. Nat. Rev. Microbiol. 5(9):710-720.
Chobot SE, Hernandez HH, Drennan CL, Elliott SJ. (2007) Direct Electrochemical Characterization of Archeael Thioredoxins. Angew. Chem. Int. Ed. Engl. 46(22):4145-4147.
Doukov TI, Hemmi H, Drennan CL, Ragsdale SW. (2007) Structural and Kinetic Evidence for an Extended Hydrogen-bonding Network in Catalysis of Methyl Group Transfer: Role of an active site asparagine residue in activation of methyl transfer by methyltransferases.J. Biol. Chem. 282(9):6609-6618.
Yeh E, Blasiak LC, Koglin A, Drennan CL, Walsh CT. (2007) Chlorination by a Long-Lived Intermediate in the Mechanism of Flavin-Dependent Halogenases. Biochemistry. 46(5):1284-1292.
Frick LE, Delaney JC, Wong C, Drennan CL, Essigmann JM. (2007) Alleviation of 1,N6-ethanoadenine genotoxicity by the Escherichia coli adaptive response protein AlkB. Proc. Natl. Acad. Sci. U.S.A. 104(3):755-760.
Blasiak LC, Vaillancourt FH, Walsh CT, Drennan CL. (2006) Crystal structure of the non-haem iron halogenase SyrB2 in syringomycin biosynthesis. Nature. 440:368-371.
Schreiter ER, Wang SC, Zamble DB, Drennan CL. (2006) NikR-operator Complex Structure and the Mechanism of Repressor Activiation by Metal Ions. Proc. Natl. Acad. Sci. U.S.A. 103(37):13676-13681.
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