 Professor, Born 1969
Diploma 1993, University of Bern, Switzerland
Ph.D. 1996, University of Bern, Switzerland
Room: 6211a
Phone: 608-265-9056
Email: brunold@chem.wisc.edu
Position: Professor
Liptak, M. D.; Datta, S.; Matthews, R.; Brunold, T. C. "Spectroscopic Study of the Cobalamin-Dependent Methionine Synthase in the Activation Conformation: Effects of the Y1139 Residue and S-Adenosylmethionine on the B12 Cofactor", J. Am. Chem. Soc. 2008, 130, 16374-16381. Park, K.; Mera, P.; Escalante-Semerena, J. C.; Brunold, T. C. "Kinetic and Spectroscopic Studies of the ATP:Corrinoid Adenosyltransferase PduO from Lactobacillus reuteri: Insights into Substrate Specificity and Mechanism of Co(II)corrinoid Reduction", Biochemistry 2008, 47, 9007-9015.
Grove, L. E.; Xie, J.; Yikilmaz, E.; Karapetyan, A.; Miller, A.-F.; Brunold, T. C. "Spectroscopic and Computational Insights into Second Sphere Amino Acid Tuning of Substrate Analogue/Active Site Interactions in Iron(III) Superoxide Dismutase", Inorg. Chem. 2008, 47, 3993-4004.
Liptak, M. D.; Fleischhacker, A. S.; Matthews, R.; Brunold, T. C. "Probing the Role of the Histidine 759 Ligand in Cobalamin-Dependent Methionine Synthase", Biochemistry 2007, 46, 8024-8035.
Fiedler, A. T.; Brunold, T. C. "Spectroscopic and Computational Studies of Ni3+ Complexes with Mixed S/N Ligation: Implications for the Active-Site of Ni Superoxide Dismutase", Inorg. Chem. 2007, 46, 8511-8523 (featured on cover).
Liptak, M. D.; Brunold, T. C. "Spectroscopic and Computational Studies of Co1+Cobalamin: Spectral and Electronic Properties of the "Superreduced" B12 Cofactor", J. Am. Chem. Soc. 2006, 128, 9144-9156. Stich, T. A.; Seravalli, J.; Venkateshrao, S.; Spiro, T. G.; Ragsdale, S. W.; Brunold, T. C. "Spectroscopic Studies of the Corrinoid/Iron-Sulfur Protein from Moorella thermoacetica", J. Am. Chem. Soc. 2006, 128, 5010-5020. Brooks, A. J.; Vlasie, M.; Banerjee, R.; Brunold, T. C. "Co-C Bond Activation in Methylmalonyl-CoA Mutase by Stabilization of the Post-homolysis Product Co2+Cobalamin", J. Am. Chem. Soc. 2005, 127, 16522-16528. Stich, T. A.; Yamanishi, M.; Banerjee, R.; Brunold, T. C. "Spectroscopic Evidence for the Formation of a Four-Coordinate Co2+Cobalamin Species Upon Binding to the Human ATP:Cobalamin Adenosyltransferase", J. Am. Chem. Soc. 2005, 127, 7660-7661. Stich, T. A.; Buan, N. R.; Escalante-Semerena, J.; Brunold, T. C. "Spectroscopic and Computational Studies of the ATP:corrinoid Adenosyltransferase (CobA) from Salmonella enterica: Insights into the Mechanism of Adenosylcobalamin", J. Am. Chem. Soc. 2005, 127, 8710-8719. Fiedler, A. T.; Bryngelson, P. A.; Maroney, M. J.; Brunold, T. C. "Spectroscopic and Computational Studies of Ni Superoxide Dismutase: Electronic Structure Contributions to Enzymatic Function", J. Am. Chem. Soc. 2005, 127, 5449-5462. Craft, J. L.; Mandimutsira, B. S.; Fujita, K.; Riordan, C. G.; Brunold, T. C. "Spectroscopic Studies of a Ni1+"CO Model Complex: Implications for the CO Dehydrogenase and Acetyl-CoA Synthase Catalytic Mechanisms", Inorg. Chem., 2003, 43, 859-867. "Spectroscopic and Computational Study of a Non-Heme Iron {Fe-NO}7 System: Exploring the Geometric and Electronic Structures of the Nitrosyl Adduct of Iron Superoxide Dismutase", J. Am. Chem. Soc., 2003, 125, 13962-13963. Stich, T. A.; Brooks, A. J.; Brunold, T. C. "Spectroscopic and Computational Studies of Co3+-Corrinoids: Spectral and Electronic Properties of the B12 Cofactors and Biologically Relevant Precursors", submitted to J. Am. Chem. Soc., 2003, 125, 5897-5914. Maliekal, J.; Karapetian, A.; Vance, C.; Yikilmaz, E.; Wu, Q.; Jackson, T. A.; Brunold, T. C.; Spiro, T. G.; Miller, A.-F. "Comparison and Contrasts between the Active Site pKs of Mn-Superoxide Dismutase and Those of Fe-Superoxide Dismutase", J. Am. Chem. Soc., 2002, 124, 15064-15075. Craft, J. L.; Ludden, P. W.; Brunold, T. C. "Spectroscopic Studies of Nickel-Deficient Carbon Monoxide Dehydrogenase from Rhodospirillum rubrum: Nature of the FeS Clusters", Biochemistry 2002, 41, 1681-1688. Yikilmaz, E.; Xie, J.; Brunold, T. C.; Miller, A.-F. "Hydrogen-Bond-Mediated Tuning of the Redox Potential of the Non-Heme Fe Site of Superoxide Dismutase", J. Am. Chem. Soc. 2002, 124, 3482-3483. Xie, J.; Yikilmaz, E.; Miller, A.-F.; Brunold, T. C. "Second-Sphere Contributions to Substrate-Analog Binding in Iron(III) Superoxide Dismutase", J. Am. Chem. Soc. 2002, 124, 3769-3774. Jackson, T. A.; Xie, J.; Yikilmaz, E.; Miller, A.-F.; Brunold, T. C. "Spectroscopic and Computational Studies on Iron and Manganese Superoxide Dismutases: Nature of the Chemical Events Associated with Active Site pKs", J. Am. Chem. Soc. 2002, 124, 10833-10845. Schenker, R.; Mandimutsira, B. S.; Riordan, C. G.; Brunold, T. C. "Spectroscopic and Computational Studies on [(PhTttBu)2Ni2("-O)2]: Nature of the Bis-oxo (Ni3+)2 Diamond Core", J. Am. Chem. Soc. 2002, 124, 13842-13855.
| Research Description
The research carried out in my laboratory is aimed at elucidating the geometric and electronic properties, and thus the reactivity, of metal centers in proteins and cofactors through combined spectroscopic and computational studies of key enzymatic states and synthetic inorganic model complexes. The spectroscopic techniques used in this research include electronic absorption, circular dichroism, magnetic circular dichroism, resonance Raman, and electron paramagnetic resonance. These experimental techniques are complemented by density functional theory and combined quantum mechanics/molecular mechanics electronic structure calculations to develop experimentally validated bonding descriptions. With this combined spectroscopic/computational approach we can selectively probe the geometric and electronic properties of catalytically active metal centers in proteins and model complexes and also explore the natures of catalytic intermediates that are inaccessible to structural studies using X-ray crystallography.
One area of research in my laboratory is devoted to the study of the known bio-organometallic cofactors, which include the enzymatically active forms of vitamin B12, adenosylcobalamin and methylcobalamin, and the Ni-containing F430 species. While structurally related to the well-characterized hemes, these cofactors employ macrocyclic ligands (termed corrin and hydrocorphin, respectively) that are substantially more reduced than the porphyrin ring, offering them considerably more conformational freedom. The mechanistic significance of this increased flexibility in the catalytic cycles of B12- and NiF430-dependent enzymes remains a subject of intense debate.
A second project pursued in my laboratory aims at exploring the geometric and electronic prerequisites for the high catalytic activities of Ni-, Fe- and Mn-dependent superoxide dismutases (SODs) that protect aerobic organisms from oxidative damage mediated by the superoxide radical anion. The Ni-dependent enzyme has only recently been isolated from some Streptomyces species, and X-ray crystallographic data have revealed that NiSOD is structurally unrelated to the other SODs. Conversely, the Fe- and MnSODs from E. coli possess virtually identical protein folds and active-site geometries; however, they are strictly metal specific. Though small differences in the second coordination spheres (comprising amino acid residues that are not directly bound to the active-site metal ion) do exist between these two enzymes, their relationship to this extraordinary metal-ion specificity remains incompletely understood.
A third major research focus of my laboratory is directed toward elucidating the electronic properties and catalytic mechanisms of enzymes possessing polynuclear NiFeS active-site clusters, including ACS and CODH that catalyze the reversible oxidation of CO to CO2 and the synthesis of acetyl-CoA from CO, CoA, and a methyl group, respectively. While high-resolution X-ray structures have recently been solved for CODH and bifunctional ACS/CODH enzymes, fundamental questions concerning the redox states, substrate binding sites, and the natures of catalytically relevant reaction intermediates of these highly elaborate polynuclear active sites have yet to be answered.
Last updated: January 20, 2009.
2009 Romnes Award 2003 NSF-CAREER Award 2003 Sloan Foundation Fellow 2003 Swiss Chemical Society: Alfred Werner Award 2000 University of Bern, Switzerland: Theodor Kocher Award 2000 Research Corporation Innovation Award 1997 University of Bern, Switzerland: Faculty Award for Ph.D. Thesis
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