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Brian M. Hoffman

Chemistry, Molecular Biosciences
PhD, California Institute of Technology

Email: bmh@northwestern.edu
Phone: (847) 491-3104
Fax: 847) 491-7713
Room: Tech NG91


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Research Interests

Long-range interprotein electron transfer; ENDOR of metalloenzymes

We have discovered that long-range electron transfer between proteins can be studied by substituting zinc protoporphyrin for heme in one of the partners of a protein-electron transfer complex. Electron transfer is initiated by flash photoproduction of the zinc protoporphyrin triplet state, which reduces its ferriheme partner by a long-range tunneling process. Mixed-metal (Zn, Fe) hybrid hemoglobins exhibit electron transfer between redox centers that are in a crystallographically known protein environment and are separated by protein residues at a metal-metal distance of 25.

We are applying this approach to physiological electron transfer reactions, such as between yeast cytochrome c peroxidase (CCP) and cytochrome c (cyt c). However, this complex is not conformationally rigid. The use of different cyt c species and of site-directed mutagenesis to vary individual residues of cyt c gives a precise means of investigating both the role of the protein matrix in electron transfer and the influence of conformational dynamics at the protein-protein interface.

Electron-nuclear double resonance (ENDOR) is a technique that combines NMR and EPR. Studies of native and isotopically enriched metalloenzymes hold the promise of individually characterizing every atom of the catalytically active metal center. The systems we are studying include peroxidases, copper proteins containing the blue-copper center, and proteins that contain multimetal centers such as aconitase, cytochrome oxidase, and hydrogenase. Our work includes the development of multifrequency CW and pulsed (nsec) ENDOR spectrometers.

Selected Publications

Responses of Mn2+ speciation in Deinococcus radiodurans and Escherichia coli to γ-radiation by advanced paramagnetic resonance methods. Sharma A, Gaidamakova EK, Matrosova VY, Bennett B, Daly MJ, and Hoffman BM. PNAS. 2013 April 9;110(15):5945-5950.

Nitrogenase: A Draft Mechanism. Hoffman BM, Lukoyanov D, Dean DR, and Seefeldt LC. Accounts of Chemical Research. 2013 February 19;46(2):587-595.

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 JH, Perera R, and Hoffman BM. Biochemistry. 2013 January 29;52(4):667-671.

EPR and 57Fe ENDOR investigation of 2Fe ferredoxins from Aquifex aeolicus. Cutsail GE, Doan PE, Hoffman BM, Meyer J, and Telser J. Journal of Biological Inorganic Chemistry. 2012 December;17(8):1137-1150.

Evolving the [Myoglobin, Cytochrome b5] Complex from Dynamic toward Simple Docking: Charging the Electron Transfer Reactive Patch. Trana EN, Nocek JM, Knutson AK, and Hoffman BM. Biochemistry. 2012 October 30;51(43):8542-8553.

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 AA, Strushkevich NV, Usanov SA, and Hoffman BM. Journal of the American Chemical Society. 2012 October 17;134(41):17149-17156.

Characterization of a Cobalt-Specific P1B-ATPase. Zielazinski EL, Cutsail GE, Hoffman BM, Stemmler TL, and Rosenzweig AC. Biochemistry. 2012 October 9;51(40):7891-7900.

Evidence for Oxygen Binding at the Active Site of Particulate Methane Monooxygenase. Culpepper MA, Cutsail GE, Hoffman BM, and Rosenzweig AC. Journal of the American Chemical Society. 2012 May 9;134(18):7640-7643.

Unification of reaction pathway and kinetic scheme for N2 reduction catalyzed by nitrogenase. Lukoyanov D, Yang Z-Y, Barney BM, Dean DR, Seefeldt LC, and Hoffman BM. PNAS. 2012 April 10;109(15):5583-5587.

Crystal Structure and Characterization of Particulate Methane Monooxygenase from Methylocystis species Strain M. Smith SM, Rawat S, Telser J, Hoffman BM, Stemmler TL, and Rosenzweig AC. Biochemistry. 2011 November 29;50(47):10231-10240.

Design, Implementation, Simulation, and Visualization of a Highly Efficient RIM Microfluidic Mixer for Rapid Freeze-Quench of Biological Samples. Schmidt B, Mahmud G, Soh S, Kim SH, Page T, O'Halloran TV, Grzybowski BA, and Hoffman BM. Applied Magnetic Resonance. 2011 August;40(4):415-425.

View all publications by Brian M. Hoffman listed in the National Library of Medicine (PubMed).