个人简介

B.S., 1978, Univ. of Illinois Ph.D., 1983, Univ. of California, Berkeley Postdoctoral Fellow, 1983-85, Albert Einstein College of Medicine Associate Director, 1985-89, NIH Pulsed EPR Research Resource AwardOrganizationDivisionLevel CodeType CodeStart DateEnd Date CNS Distinguished Faculty AwardProfessionalHonors2012 MemberNational Institutes of HealthNIH Special Study SectionsProfessionalProfessional Activities20002002 University Teacher-Scholar AwardMichigan State UniversityProfessionalHonors1997 MemberNational Institutes of HealthNIH Metallobiochemistry Study SectionProfessionalProfessional Activities19962000 MemberNational Institutes of HealthNIH Special Study SectionsProfessionalProfessional Activities19951996 Teacher-Scholar AwardMichigan State UniversityCollege of Natural ScienceProfessionalHonors1995 Officer, MSU Local SectionAmerican Chemical SocietyProfessionalProfessional Activities19922004 MemberNational Institutes of HealthNIH Special Study SectionsProfessionalProfessional Activities19901991 NIH National Pulsed EPR Research Resource Governing BoardNational Institutes of HealthProfessionalProfessional Activities19851999 Ph.D.University of California, BerkeleyGraduateDegree1983 Chancellor's Fellow in ChemistryUniversity of California, BerkeleyGraduateFellowship1981 Bachelor of Science with Highest Distinction in ChemistryUniversity of Illinois, Urbana-ChampaignUndergraduateDegree1978 Edmund James ScholarUniversity of Illinois, Urbana-ChampaignUndergraduateHonors19741978 ChairpersonMichigan State UniversityDepartment of ChemistryProfessionalAdministration

研究领域

Biological Physical

(Research Description PDF - 819 kb) Electron Paramagnetic Resonance (EPR) spectroscopy provides an ideal tool for the determination of the structures of paramagnetic centers in chemical systems. The origin of this structural information is the spin-spin coupling between the magnetic moments of the paramagnetic center and nuclei that lie less than 6 ? away. Unfortunately, these spin-spin couplings are often weak and as such, they are buried by the inhomogeneous broadening of the EPR absorbtion lineshape. In the McCracken lab, we are applying the advanced EPR methods of Electron Spin Echo Envelope Modulation (ESEEM) and Electron-Nuclear Double Resonance (ENDOR) to determine the structures about paramagnetic centers in metalloenzymes. Our studies are aimed at using the information we gain from these experiments to understand the chemistry that occurs at metal centers and answer questions concerning structure-function relationships that cannot be addressed using other structural tools like NMR or X-ray crystallography in isolation. The figure shown below details two different applications of ESEEM spectroscopy to characterize the ligation structure of an Fe(II) ion located at the heart of the catalytic site of the enzyme Tyrosine Hydroxylase. This enzyme is present in the central nervous system of mammals and catalyzes the rate-limiting step in the biosynthesis of the catecholamine neurotransmitters, dopamine, epinephrine and norepinephrine. Our gateway into the structure is the EPR spectrum of an {FeNO}7 derivative of the enzyme and is shown in figure (a). This spectrum is about 200 mT wide and provides no features that can be attributed to ligands bound to Fe(II), or substrates and cofactors that may bind to the enzyme in Fe(II)’s second coordination sphere. Figure (b) shows 2H-ESEEM spectra, obtained at seven different magnetic field positions across the EPR spectrum, that arise from hyperfine coupling between a deuterium atom of 3,5 2H - tyrosine bound to the enzyme and the paramagnetic Fe-NO center. The amplitudes and lineshapes of these spectra can be fit to a spin Hamiltonian model to provide the location of the coupled deuteron with respect to the axis of the Fe-NO bond, and the direction of the C-2H bond associated with the labeled substrate. Figure (d) summarizes these results showing that substrate tyrosine binds so that a coupled deuteron (red ball in figure d) is positioned 4.1 ? from the Fe(II) and that the vector connecting the metal ion with this coupled deuteron makes an angle of 25° with the Fe-NO bond axis. These data represent the first structural information gained on the binding of the amino acid substrate at the catalytic site of this family of enzymes. By repeating these measurements on substrates deuterated at other positions, our crude magnetic structure can be built into an atomic level structure. The second type of experiment is a 2-dimensional ESEEM measurement that has proved useful for viewing the stronger hyperfine couplings that arise from the Fe(II) ligands. The spectrum shown in figure (c) was collected at 260 mT (aqua arrow in figure(a)) and shows off-diagonal cross-peaks, circled in red, that are diagnostic for bound water and/or hydroxide ligands.

近期论文

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Chandran, K.; McCracken, J.; Peterson, F.C.; Antholine, W.E.; Volkman, B.F.; Kalyanaraman, B. Oxidation of Histidine Residues in Copper-Zinc Superoxide Dismutase by Bicarbonate Stimulated Peroxidase and Thiol Oxidase Activities: Pulse EPR and NMR Studies, Biochemistry, 49, 10616-10622, 2010. Raththagala, M.; Karunarathne, W.; Krzyaniak, M.D.; McCracken, J. and Spence, D. Hydroxyurea stimulates the release of ATP from rabbit erythrocytes through an increase in calcium and nitric oxide production, Eur. J. Pharmacology, 645, 32-38, 2010. Mathrubootham, V.; Thomas,J.; Staples, R.; McCracken, J.; Shearer, J. and Hegg, E.L. Bis-Amide and Mono-amine/amide NiN2S2 Complexes as models for Nickel-Containing Acetyl Coenzyme Synthase and Superoxide Dismutase, Inorganic Chemistry, 49, 5393-5406, 2010. Cappillino, P.J.; Miecznikowski, J.R.; Tyler, L.A.; Lo, W.; Kasibatla, B.S.T.; Krzyaniak, M.D.; McCracken, J.; Armstrong, W.H. and Caradonna, J.P. Synthesis Characterization and Reactivity of Iron(II) and Iron (III) Compounds with fac-N2O, cis-N2O2 and N2O3 Donor Ligands: Models for the 2-His-1-Carboxylate Motif of Mononuclear Nonheme Iron Dioxygenases, Dalton Trans., Submitted 2009. Sharpe, M.A.; Krzyaniak, M.D.; Xu, S.; McCracken, J. and Ferguson-Miller, S. EPR Evidence of Cyanide Binding to the Mn(Mg) center of Cytochrome c Oxidase: Support for CuA-Mg involvement in Proton Pumping, Biochemistry, 48, 328-335 , 2009. Mills, D.A.; Xu, S.; Geren, L.; Hiser, C.; Qin, L.; Sharpe, M.A.; McCracken, J.; Durham, B.;Millett, F.; Ferguson-Miller, S. Proton Dependent Electron transfer from CuA to heme a and an Altered EPR Spectrum in Mutants Close to Heme a of Cytochrome Oxidase, Biochemistry, 47, 11499-11509 , 2008. Schrauben, J.N.; Guo, D.; McCracken, J.L. and McCusker, J. Electronic Structure of [Ga2(tren)2(CAsq,cat)](BPh4)2(BF4): An EPR, ENDOR, and Density Functional Study, Inorg. Chim. Acta, 361, 3539-3547 , 2008. Valayutham, M.; Muthukumaran, R.B.; Sostaric, J.Z.; McCracken, J. and Zweier, J.L. ESEEM Studies of Peptide Nitrogen Hyperfine Coupling in Tyrosyl Radicals and Model PeptidesA Novel Pathway for Cancer Chemoprevention : Role of Cytochrome c, Free Radical Biology and Medicine, 43, 1076-1085 , 2007. McCracken, J.; Vassiliev, I.R.; Yang, E.C.; Range, K. and Barry, B.A. ESEEM Studies of Peptide Nitrogen Hyperfine Coupling in Tyrosyl Radicals and Model Peptides, J. Phys. Chem. B, 111, 6586-6592 , 2007. Muthukumaran, R.B.; Grzyska, P.K.; Hausinger, R.P. and McCracken, J. Probing the Fe-substrate orientation for taurine/α-ketoglutarate dioxygenase using deuterium ESEEM spectroscopy, Biochemistry, 46, 5951-5959 , 2007. MirAfzali, Z.; Leipprandt, J.R.; McCracken, J.L.; and DeWitt, D.L. Topography of the Prostaglandin Endoperoxide H2 Synthase-2 in Membranes, J. Biol. Chem., 281, 28354-29364 , 2006. MirAfzali, Z.; Leipprandt, J.R.; McCracken, J.L.; and DeWitt, D.L. Fast, Efficient Reconstitution of the cyclooxygenases into Proteoliposomes, Arch. Biochem. Biophys., 443, 60-65 , 2005. Bernards, M.L.; Thelen, K.D.; Penner, D.; Muthukumaran, R.B. and McCracken, J. Glyphosate Interaction with Manganese in Tank Mixtures and its Effect of Glyphosate Adsorption and Translocation, Weed Science, 53, 787-794 , 2005. Schmidt, B.; McCracken, J. and Ferguson-Miller, S. A discrete water exit pathway for the membrane protein, cytochrome c oxidase, Proc. Natl. Acad. Sci., 100, 15539-15542 , 2003. Ryle, M.J.; Liu, A.; Muthukumaran, R.B.; Ho, R.Y.N.; McCracken, J.; Que, L. and Hausinger, R.P. Tyrosyl Radical Formation in TauD, an α-Keto Acid Dependent Non-heme Iron Dioxygenase, Biochemistry, 42, 1854-1862 , 2003. Artz, J.D.; Schmidt, B; McCracken, J.L. and Marletta, M.A. Effects of nitroglycerin on soluble Guanylate Cyclase: Implications for Nitrate Tolerance, J. Biol. Chem., 277, 18253-18256 , 2002. Schmidt, B.; Florens, L.; McCracken, J. and Ferguson-Miller, S. Fast Deuterium Exchange to the Buried Magnesium/Manganese Site in Cytochrome-c Oxidase, Biochemistry, 40, 7491-7497 , 2001. Smith, T.; McCracken, J.; Shin, Y-K. and DeWitt, D.L. Arachidonic Acid and NSAIDs Induce conformational Changes In the Human Prostaglandin Endoperoxide H2 Synthase-2 (COX-2), J. Biol. Chem., 275, 40407-40415 , 2000. Hogan, D.A.; Smith, S.R.; Saari, E.A.; McCracken, J. and Hausinger, R.P. Site-Directed Mutagenesis of 2,4-Dichlorophenoxyacetic Acid/α-Ketoglutarate Dioxygenase, J. Biol. Chem., 275, 12400-12409 , 2000. Singh, V.; Zhu, Z.; Davidson, V.L. and McCracken, J. Characterization of the Tryptophan Tryptophyl-Semiquinone Catalytic Intermediate of Methylamine Dehydrogenase by Electron Spin Echo Envelope Modulation Spectroscopy, J. Am. Chem. Soc., 122, 931-938 , 2000.