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Scholarly Interest Report
         
Graham Palmer
Professor Emeritus
 
e-mail:graham@bioc.rice.edu
 
  • B.Sc. Biochemistry (1957) University of Sheffield, Sheffield, England
  • Ph.D. Biochemistry (1962) University of Sheffield, Sheffield, England
 
Primary Department
   Department of BioSciences
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Department Affiliations
 
  • Institute of Biosciences and Bioengineering
  • Keck Center for Quantitative Biomedical Sciences
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    Research Areas
     Mechanisms of redox-active heme-proteins.
     
    Research Statement.
     

    The discipline of bioenergetics attempts to characterize the biochemical processes whereby the chemical free energy that originates with our diet is made available to living organisms. In eucaryotic systems the relevant processes are catalyzed by enzyme complexes present in the inner membrane of the mitochondrion. These enzymes implement electron transfer reactions, and the passage of electrons through the relevant enzyme complex leads to the translocation of protons across this membrane; the proton gradient so-formed is the primary energy-conserving event.


    My laboratory is involved in the characterization of one of these enzymes, namely cytochrome oxidase (Complex IV). The experimental approach depends on the application of spectroscopic and other physical methods, in conjunction with transient state kinetic experiments, to define the structures and dynamics of the species which function in the electron transport, and to a lesser extent, the proton translocation reactions. By these methods many of the stereochemical and electronic properties of the relevant redox active reactants have been defined, and specific kinetic mechanisms have been proposed and examined. A second area of current concern is the structure and reactivity of the binuclear center comprising cytochrome a3 and CuB and which is the catalytic site for the reduction of oxygen to water. This binuclear center is being studied using a combination of ligand reactivity, electron paramagnetic resonance, resonance Raman and Fourier Transform Infra-Red measurements, and a minimum of three sites for ligand reaction have already been identified. The role of these sites in the catalytic mechanism is being pursued.


    In another vein we are also studying the two-heme cytochrome b561 from chromaffin granules. This protein is part of the metabolic pathway in the biosynthesis of adrenaline (epinephrine). The mammalian protein has been expressed in insect cells, yeast and in E. coli and a variety of mutants of presumed relevance to biological function have been prepared and are currently under study. The protein is a member of a large and diverse family of mammalian proteins that include proteins involved in iron assimilation and cancer suppression. As cytochrome b561 is the best-characterized member of this family its study may throw light on the mode of action of the other members of the family.


     
    Selected Publications
     Abstracts
     

    Fabian, M., Jancura, D., and Palmer, G. "Interaction of ligands with cytochrome a in fully oxidized bovine cytochrome c oxidase." BBA EBEC Short Reports, 12 (2002) : 84.

     
     Refereed articles
     

    Liu, W., da Silva, G.F.Z., Wu,. G., Palmer, G., Tsai, A-L and Kulmacz, R. "Functional and Structural roles of residues in the third extra-membrane segment of adrenal cytochrome b561." Biochemistry, 50(15) (2011) : 3149-3160.

     
     

    Sato H, Higashimoto Y, Sakamoto H, Sugishima M, Shimokawa C, Harada J, Palmer G, Noguchi M. "Reduction of oxaporphyrin ring of CO-bound α-verdoheme complexed with heme oxygenase-1 by NADPH-cytochrome P450 reductase." J.Inorg. Biochem, 105 (2011) : 286-296.

     
     

    Tsai,A-L., Wu, G., Rogge,C.E.,Lu,J-M.,Peng S., van der Donk, W.A., Palmer, G., Gerfen, G. and Kulmacz, R. "Structural Comparisons of arachidonic acid induced radicals formed by prostaglandin H synthase-1 and 2." J. Inorg. Biochem., 105 (2011) : 248-256.

     
     

    Parul, D., Palmer, G. and Fabian M. "Ligand Trapping by Cytochrome c oxidase: Implications for Gating at the Catalytic Center." J. Biol.Chem., 285 (2010) : 4536-4543.

     
     

    Tsai,A-L., Wu, G., Rogge,C.E.,Lu,J-M.,Peng S., van der Donk, W.A., Palmer, G., Gerfen, G. and Kulmacz, R. "Structural Comparisons of arachidonic acid induced radicals formed by prostaglandin H synthase-1 and 2." J. Inorg. Biochem., 105 (2010) : 248-256.

     
     

    Kamensky, Y., Liu, W., Tsai, A.-L., Kulmacz, R.J., and Palmer, G. "Axial ligation and stoichiometry of heme centers in adrenal cytochrome b561." Biochemistry, 46 (2007) : 8647-8658.

     
     

    Liu, W., Rogge, C. E., da Silva, G. F., Shinkarev, V. P., Tsai, A. L., Kamensky, Y., Palmer, G., and Kulmacz, R. J. "His92 and His110 selectively affect different heme centers of adrenal cytochrome b561." Biochim Biophys Acta - Bioenergetics (2008) In Press

     
     

    Wu, G., Rogge, C.E., Wang, J.-S., Kulmacz, R.J., Palmer, G., and Tsai, A.-L. "Oxyferryl heme and not tyrosyl radical is the likely culprit in prostaglandin H synthase-1 peroxidase inactivation." Biochemistry, 46 (2007) : 534-542.

     
     

    Fabian, M., Jancura, D., Bona, M., Musatov, A., Baran, M., and Palmer, G. "The influence of reduction of heme a and CuA on the oxidized catalytic center of cytochrome c oxidase: Insight from organic solvents." Biochemistry, 45 (2006) : 4277-4283.

     
     

    Higashimoto, Y., Sata, H., Sakamoto, H., Takahashi, K., Palmer, G. and Noguchi, M. "The reactions of heme- and verdoheme-heme oxygenase with FMN depleted NADPH-cytochrome P450 reductase. Electrons required for verdoheme oxidation can be transferred by a pathway not involving FMN." J. Biol. Chem., 281 (2006) : 31659-31667.

     
     

    Jancura, D., Antalik, M., Berka, V., Palmer, G., and Fabian, M. "Filling the catalytic site of cytochrome c oxidase with electrons: Reduced CuB facilitates internal electron transfer to heme a3." J. Biol. Chem, 281 (2006) : 20003-20010.

     
     

    Jancura, D., Berka, V., Antalik, M., Bagelova, J., Gennis, R. G., Palmer, G., and Fabian, M. "Spectral and kinetic equivalence of oxidized cytochrome c oxidase as isolated and ‘activated’ by reoxidation." J. Biol. Chem, 281 (2006) : 30219-30325.

     
     

    Antalik, M., Palmer, G., and Fabian, M. "A role for protein in internal electron transfer to the catalytic center of cytchrome c oxidase." Biochemistry, 44 (2005) : 14881-14889.

     
     

    Higashimoto, Y., Sakamoto, H., Hayashi, S., Sugishima, M., Fukuyama, K, Palmer, G., and Noguchi, M. "Involvement of NADP(H) in the interaction between heme oxygenase-1 and cytochrome P450 reductase." J. Biol. Chem., 280 (2005) : 729-737.

     
     

    Liu, W., Kamensky, Y., Kakkar, R., Foley, E., Kulmacz, R.J., and Palmer, G. "Purification and characterization of the bovine adrenal cytochrome b561 expressed in insect and yeast cell systems." Protein Expression and Purification, 40 (2005) : 429-439.

     
     

    Parul, D., Palmer, G., and Fabian, M. "Proton interactions with hemes a and a3 in bovine heart cytochrome c oxidase." Biochemistry, 44 (2005) : 4562-4571.

     
     

    Sakamoto, H., Takahashi, K., Higashimoto, Y., Harada, S., Palmer, G., and Noguchi, M. "A kinetic study of the mechanism of conversion of alpha-hydroxyheme to verdoheme while bound to heme oxygenase." Biochemical and Biophysical Research Communications, 338 (2005) : 578-583.

     
     

    Berka, B., Wu, G., Yeh, H.C., Palmer, G., and Tsai, A.-L. "Three different oxygen induced radicals in eNOS oxygenase under regulation by L-argininine and tetrahydrobiopterin." J. Biol. Chem., 279 (2004) : 32243-32251.

     
     

    Fabian, M., Jancura, D., and Palmer, G. "Two sites of interaction of anions with cytochrome a in oxidized bovine cytochrome c oxidase." J. Biol Chem., 279 (2004) : 16170-16177.

     
     

    Fabian, M., Skultety, L., Jancura, D., and Palmer, G. "Implications of ligand binding studies for the catalytic mechanism of cytochrome c oxidase." Biochim. Biophys. Acta, 1655 (2004) : 298-305.

     
     

    Liu, W., Rogge., C.E., Bambai, B., Palmer, G., Tsai, A.-L., and Kulmacz, R.J. "Characterization of the heme environment in Arabidopsis thaliana fatty acid alpha-dioxygenase." J. Biol. Chem., 279 (2004) : 29805-29815.

     
     

    McMahon, B.J., Fabian, M., Tomson, F., Causgrove, T., Bailey, J.A., Rein, F.N., Dyer, R.B., Palmer, G., Gennis, R.B., and Woodruff, W.H. "FTIR studies of internal proton transfer reactions linked to inter-heme electron transfer in bovine cytochrome c oxidase." Biochim. Biophys. Acta, 1655 (2004) : 321-331.

     
     

    Palmer, G. "The contributions of G.T. (Jerry) Babcock to our understanding of cytochrome oxidase." Biochim. Biophys. Acta, 1655 (2004) : 235-240.

     
     

    Sakamoto, H., Higashimoto, Y., Hayashi, S., Sugishima, M., Fukuyama, K., Palmer, G., and Noguchi, M. "Hydroxylamine and hydrazine bind directly to the heme iron of the heme-heme oxygenase-1 complex." J. BioInorganic Chem., 98 (2004) : 1223-1229.

     
     

    Fabian, M., Skultety, L., Brunel, C., and Palmer, G. "The Cyanide Stimulated Dissociation of Chloride from the Catalytic Center of Cytochrome c Oxidase." Biochemistry, 40 (2001) : 6061-6069.

     
     

    Fabian, M., and Palmer G. "Proton Involvement in the Redox Transition from the "Peroxy" to the Ferryl Intermediate of Cytochrome c Oxidase." Biochemistry, 40 (2001) : 1867-1874.

     
     

    Morgan, J., Verkohvsky, M., Palmer, G., and Wikstrom, M. "The Role of the Pr Intermediate in the Reaction of Cytochrome c Oxidase with Oxygen." Biochemistry, 40 (2001) : 6882-689.

     
     Other
     

    Kamensky, Y., and Palmer, G. "Chromaffin Granule Membranes Contain at Least Three Heme Centers: Direct Evidence from EPR and Absorption Spectroscopy." FEBS Letters, 491 (2001) : 119-122.

     
     

    Palmer, G. "Electron Paramagnetic Resonance of Metalloproteins." in Physical Methods in BioInorganic Chemistry (L. Que, ed.), University Press (2000) : 121-185.

     
     

    Sakamoto, H., Omata, Y., Adachi, Y., Palmer, G., and Noguchi M. "Separation and Identification of the Regioisomers of Verdoheme by Reversed-Phase Ion-Pair High-Performance Liquid Chromatography and Characterization of their Complexes with Heme Oxygenase." J. Inorg. Biochem., 82 (113-121) : 2000.

     
     

    Shi, W., Hoganson, C.W., Espe, M., Bender, C.J., Babcock, G.T., Palmer, G., Kulmacz, R.J., and Tsai, A.-L. "EPR and ENDOR Spectroscopic Identification and Characterization of Tyrosyl Radicals in Prostaglandin H Synthase." Biochemistry, 39 (2000) : 4112-4121.

     
     

    Fabian, M., Wong, W.W., Gennis, R.B., and Palmer, G. "Mass Spectrometric Determination of Dioxygen Bond Splitting in the "Peroxy" Form of Cytochrome c Oxidase." Proc. Natl. Acad. Sci. USA, 96 (1999) : 13114-13117.

     
     

    Fabian, M., and Palmer, G. "The Redox State of Peroxy and Ferryl Intermediates in Cytochrome c Oxidase Catalysis." Biochemistry, 38 (1999) : 6270-6275.

     
     

    Sakamoto, H., Omata, Y., Palmer, G., and Noguchi, M. "Ferric Alpha-hydroxyheme Bound to Heme Oxygenase Can Be Converted to Verdoheme by Dioxygen in the Absence of Added Reducing Equivalents." J. Biol. Chem., 274 (1999) : 18196-18200.

     
     

    Tsai, A-L., Wu, G., Palmer, G., Bambai, B., Koehn, J.A., Marshall, P., and Kulmacz, R.J. "Rapid Kinetics of Tyrosyl Radical Formation and Heme Redox State in Prostaglandin H Synthase-1 and -2." J. Biol. Chem., 274 (1999) : 21695-21700.

     
     

    Berka, V., Palmer, G., Chen, P.-F., and Tsai, A.-L. "The Effects of Various Imidazole Ligands on Heme Conformation in Endothelial Nitric Oxide Synthase." Biochemistry, 37 (1998) : 6136-6144.

     
     

    Fabian, M., and Palmer, G. "Hydrogen Peroxide Is Not Released Following Reaction of Cyanide with Several Catalytically Important Derivatives of Cytochrome c Oxidase." FEBS Lett., 442 (1998) : 1-4.

     
     

    Liao, G., and Palmer, G. "Diazene -- A Not So Innocent Ligand for the Binuclear Center of Cytochrome Oxidase." Biochemistry, 37 (1998) : 15583-15592.

     
     

    Palmer, G. "The Electronic Structure of the His-Tyr Adduct Present at the Binuclear Center of Cytochrome c Oxidase." EBEC Short Reports, 10 (1998) : 94.

     
     

    Tsai, A.-L., Berka, V., Kulmacz, R.J., Wu, G., and Palmer, G. "An Improved Packing Device for Rapid Freeze-trap EPR Kinetic Measurements." Anal. Biochem., 264 (1998) : 165-171.

     
     

    Tsai, A.L., Palmer, G., Xiao, G., Swinney, D.C., and Kulmacz, R.J. "Structural Characterization of Arachidonyl Radicals formed by Prostaglandin H Synthase-2 and Prostaglandin H Synthase-1 Reconstituted with Mangano Protoporphyrin IX." J. Biol. Chem., 273 (1998) : 3888-3894.

     
    Presentations
     Other
     

    "Cytochrome Oxidase -- From Spectroscope to Synchrotron." Invited speaker, Department of Biochemistry & Cell Biology, Rice University, Houston, Texas. (December 7, 1998)

     
     

    "What Do We Understand about the Catalytic Intermediates of Cytochrome Oxidase?." Invited speaker, University of California, San Francisco, California. (April 24, 1998)