Faculty

Brian Hoffman, PhD

Professor
Chemistry
PhD, Caltech

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

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 metaloenzymes 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

Varying the Electrochemical Potential and Thickness of Porphyrazine SAMs by Molecular Design. Zong H, Sun P, Mirkin CA, Barrett AG, Hoffman BM. J Phys Chem B. 2009 Oct 19. [Epub ahead of print] 

EPR and ENDOR characterization of the reactive intermediates in the generation of NO by cryoreduced oxy-nitric oxide synthase from Geobacillus stearothermophilus. Davydov R, Sudhamsu J, Lees NS, Crane BR, Hoffman BM. J Am Chem Soc. 2009 Oct 14;131(40):14493-507. 

Electrostatic redesign of the [myoglobin, cytochrome b5] interface to create a well-defined docked complex with rapid interprotein electron transfer. Xiong P, Nocek JM, Griffin AK, Wang J, Hoffman BM. J Am Chem Soc. 2009 May 27;131(20):6938-9. 

Identification of Protonated Oxygenic Ligands of Ribonucleotide Reductase Intermediate X. Shanmugam M, Doan PE, Lees NS, Stubbe J, Hoffman BM. J Am Chem Soc. 2009 Feb 16. [Epub ahead of print] 

Characterization of the microsomal cytochrome P450 2B4 O2 activation intermediates by cryoreduction and electron paramagnetic resonance. Davydov R, Razeghifard R, Im SC, Waskell L, Hoffman BM. Biochemistry. 2008 Sep 9;47(36):9661-6. Epub 2008 Aug 13. 

“Connecting nitrogenase intermediates with the kinetic scheme for N2 reduction by a relaxation protocol and identification of the N2 binding state,” Lukoyanov, D.; Barney, B. M.; Dean, D. R.; Seefeldt, L. C.; Hoffman, B. M. Proc. Natl. Acad. Sci. 2007, 104, 1451-1455.

"Dynamic Docking of Cytochrome b5 with Myoglobin and α-Hemoglobin: Heme-Neutralization 'Squares' and the Binding of Electron-Transfer-Reactive Configurations," Wheeler, K. E.; Nocek, J.; Cull, D. A.; Yatsunyk, L. A.; Rosenzweig, A. C.; Hoffman, B. M. J. Am. Chem. Soc. 2007, 129, 3906-3917.

"Breaking the N2 triple bond: insights into the nitrogenase mechanism," Barney, B. M.; Lee, H.-I.; Dos Santos, P. C.; Hoffman, B. M.; Dean, D. R.; Seefeldt, L. C. Dalton Transactions 2006, 2277-2284.

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