Brian M. Hoffman Professor of Chemistry, Molecular Biosciences

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

Charge-Disproportionation Symmetry Breaking Creates a Heterodimeric Myoglobin Complex with Enhanced Affinity and Rapid Intracomplex Electron Transfer. Trana EN, Nocek JM, Vander Woude J, Span I, Smith SM, Rosenzweig AC, and Hoffman BM. Journal of the American Chemical Society. 2016 September 28;138(38):12615-12628.

Characterization of Methanobactin from Methylosinus sp. LW4. Kenney GE, Goering AW, Ross MO, DeHart CJ, Thomas PM, Hoffman BM, Kelleher NL, and Rosenzweig AC. Journal of the American Chemical Society. 2016 September 7;138(35):11124-11127.

CO2 Reduction Catalyzed by Nitrogenase: Pathways to Formate, Carbon Monoxide, and Methane. Khadka N, Dean DR, Smith D, Hoffman BM, Raugel S, and Seefeldt LC. Inorganic Chemistry. 2016 September 6;55(17):8321-8330.

Reductive Elimination of H2 Activates Nitrogenase to Reduce the N≡N Triple Bond: Characterization of the E4(4H) Janus Intermediate in Wild-Type Enzyme. Lukoyanov D, Khadka N, Yang Z-Y, Dean DR, Seefeldt LC, and Hoffman BM. Journal of the American Chemical Society. 2016 August 24;138(33):10674-10683.

Organometallic Complex Formed by an Unconventional Radical S-Adenosylmethionine Enzyme. Dong M, Horitani M, Dzikovski B, Pandelia M-E, Krebs C, Freed JH, Hoffman BM, and Lin H. Journal of the American Chemical Society. 2016 August 10;138(31):9755-9758.

Ultrafast Excited State Relaxation of a Metalloporphyrin Revealed by Femtosecond X-ray Absorption Spectroscopy. Shelby ML, Lestrange PJ, Jackson NE, Haldrup K, Mara MW, Stickrath AB, Zhu D, Lemke HT, Chollet M, Hoffman BM, Li X, and Chen LX. Journal of the American Chemical Society. 2016 July 20;138(28):8752-8764.

Radical SAM catalysis via an organometallic intermediate with an Fe–[5 -C]-deoxyadenosyl bond. Horitani M, Shisler K, Broderick WE, Hutcheson RU, Duschene KS, Marts AR, Hoffman BM, and Broderick JB. Science. 2016 May 13;352(6287):822-825.

Role of the Proximal Cysteine Hydrogen Bonding Interaction in Cytochrome P450 2B4 Studied by Cryoreduction, Electron Paramagnetic Resonance, and Electron–Nuclear Double Resonance Spectroscopy. Davydov R, Im S, Shanmugam M, Gunderson WA, Pearl NM, Hoffman BM, and Waskell L. Biochemistry. 2016 February 16;55(6):869-883.

Spectroscopic and Crystallographic Evidence for the Role of a Water-Containing H-Bond Network in Oxidase Activity of an Engineered Myoglobin. Petrik ID, Davydov R, Ross M, Zhao X, Hoffman B, and Lu Y. Journal of the American Chemical Society. 2016 February 3;138(4):1134-1137.

Reversible Photoinduced Reductive Elimination of H2 from the Nitrogenase Dihydride State, the E4(4H) Janus Intermediate. Lukoyanov D, Khadka N, Yang Z-Y, Dean DR, Seefeldt LC, and Hoffman BM. Journal of the American Chemical Society. 2016 February 3;138(4):1320-1327.

Comparison of the Mechanisms of Heme Hydroxylation by Heme Oxygenases-1 and -2: Kinetic and Cryoreduction Studies. Davydov R, Fleischhacker AS, Bagai I, Hoffman BM, and Ragsdale SW. Biochemistry. 2016 January 12;55(1):62-68.

View all publications by Brian M. Hoffman listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.