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Brian Hoffman


B.S.: University of Chicago; Ph.D.: California Institute of Technology

Research Statement

We determine the catalytic mechanisms of metalloenzymes through the development and implementation of electron-nuclear double resonance (ENDOR) spectroscopy, a combination of NMR and EPR. This technique is uniquely able to determine active site composition, electronic and geometric structures, not merely for the resting state but, most importantly, for key trapped catlalytic intermediates. This approach is applied to complex multi-metallic catalytic centers, as in the globally important enzyme, nitrogenase, which provides nitrogen as nutrient for most of the planet, as well as to key mononuclear centers, as in the physiologically vital heme enzymes nitric oxide synthase and cytochrome P450.  In parallel, we study biomimetic complexes that  provide constraints that help identify intermediates trapped during catalysis, and that are moreover of intrinsic importance as Jahn-Teller active systems whose H2 complexes exhibit novel dynamic properties. A second area of research is the study of long-range electron transfer between proteins. We focus on the central question: how do conformational dynamics at a protein-protein interface control inter-protein electron transfer? As protein-protein interactions are central to almost all biological processes, this focus links our research to other major problems in biology.

Selected Publications

"Mechanism of Nitrogen Fixation by Nitrogenase: The Next Stage," Hoffman, B. M.; Lukoyanov, D.; Yang, Z. Y.; Dean, D. R.; Seefeldt, L. C.,. Chem Rev 2014, 114 (8), 4041-62.

"Free H2 Rotation Vs Jahn-Teller Constraints in the Nonclassical Trigonal (Tpb)Co-H2 Complex," Gunderson, W. A.; Suess, D. L.; Fong, H.; Wang, X.; Hoffmann, B. M.; Cutsail III, G. E.; Peters, J. C.; Hoffman, B. M.,. J. Am. Chem. Soc. 2014, 136 (42), 14998-5009.

"Symmetrized Photoinitiated Electron Flow within the [Myoglobin:Cytochrome b5] Complex on Singlet and Triplet Time Scales: Energetics Vs Dynamics Petlakh," Co, N.; Young, R. M.; Smeigh, A. L.; Wasielewski, M. R.; Hoffman, B.M., J. Am. Chem. Soc. 2014, In Press.

"Enzymatic and Cryoreduction EPR Studies of the Hydroxylation of Methylated Nω-Hydroxy-L-Arginine Analogues by Nitric Oxide Synthase from Geobacillus stearothermophilus," Davydov, R.; Labby, K. J.; Chobot, S. E.; Lukoyanov, D. A.; Crane, B. R.; Silverman, R. B.; Hoffman, B. M., Biochemistry 2014, 53 (41), 6511-9.

"Nitrite and Hydroxylamine as Nitrogenase Substrates: Mechanistic Implications for the Pathway of N2 Reduction," Shaw, S.; Lukoyanov, D.; Danyal, K.; Dean, D. R.; Hoffman, B. M.; Seefeldt, L. C.,. J. Am. Chem. Soc. 2014, 136 (36), 12776-83.

"EPR, ENDOR, and Electronic Structure Studies of the Jahn-Teller Distortion in an Fe(V) Nitride," Cutsail III, G. E.; Stein, B. W.; Subedi, D.; Smith, J. M.; Kirk, M. L.; Hoffman, B. M.,. J. Am. Chem. Soc. 2014, 136 (35), 12323-36.

"Responses of Mn2+ Speciation in Deinococcus radiodurans and Escherichia coli to Gamma-Radiation by Advanced Paramagnetic Resonance Methods," Sharma, A.; Gaidamakova, E. K.; Matrosova, V. Y.; Bennett, B.; Daly, M. J.; Hoffman, B. M.,. PNAS 2013, 110 (15), 5945-50.

"Distance-Independent Charge Recombination Kinetics in Cytochrome c-Cytochrome c Peroxidase Complexes: Compensating Changes in the Electronic Coupling and Reorganization Energies," Jiang, N.; Kuznetsov, A.; Nocek, J. M.; Hoffman, B. M.; Crane, B. R.; Hu, X.; Beratan, D. N.,. J. Phys. Chem. B 2013, 117 (31), 9129-41.

"The Use of Deuterated Camphor as a Substrate in 1H Endor Studies of Hydroxylation by Cryoreduced Oxy P450cam Provides New Evidence of the Involvement of Compound I," Davydov, R.; Dawson, J. H.; Perera, R.; Hoffman, B. M.,. Biochemistry 2013, 52 (4), 667-71.

"Evolving the [Myoglobin, Cytochrome b5] Complex from Dynamic toward Simple Docking: Charging the Electron Transfer Reactive Patch," Trana, E. N.; Nocek, J. M.; Knutson, A. K.; Hoffman, B. M.,. Biochemistry 2012, 51 (43), 8542-53.

"Modeling the Signatures of Hydrides in Metalloenzymes: Endor Analysis of a Di-Iron Fe(μ-NH)(μ-H)Fe Core," Kinney, R. A.; Saouma, C. T.; Peters, J. C.; Hoffman, B. M.,. J. Am. Chem. Soc. 2012, 134 (30), 12637-47.

"Compound I Is the Reactive Intermediate in the First Monooxygenation Step During Conversion of Cholesterol to Pregnenolone by Cytochrome P450scc: EPR/ENDOR/Cryoreduction/Annealing Studies," Davydov, R.; Gilep, A. A.; Strushkevich, N. V.; Usanov, S. A.; Hoffman, B. M.,. J. Am. Chem. Soc. 2012, 134 (41), 17149-56.

Selected Honors/Awards

  • Member, National Academy of Sciences
  • Ritter Lecturer, Miami University (2013)
  • ACS F.A Cotton Medal for Excellence in Chemical Research (2013)
  • RSC Joseph Chatt Award (2012)
  • Alfred Bader Award in Bioinorganic or Bioorganic Chemistry (2012)
  • Fellow, International Society of Magnetic Resonance (ISMAR) (2009)
  • Frontiers in Biological Chemistry Award (2008)
  • Zavoisky Prize from the Russian Academy of Sciences (2007)
  • Charles E. and Emma H. Morrison Professor of Chemistry (2007)
  • Fellow, American Association for the Advancement of Science
  • Fellow, American Academy of Arts & Sciences (2002)
  • Gold Medal International EPR Society (IES) (1999)
  • Bruker Prize, Royal Society of Chemistry (1997)
  • Chair, Bioinorganics Subdivision, American Chemical Society (1991-93)
  • Chair, NIH-BMT Study Section (1990-92)
  • Career Development Award, National Institutes of Health (1972-77)
  • Alfred P. Sloan Fellow (1971-73)
  • NAS-NRC Fellow, Massachusetts Institute of Technology
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