Hemes are among the most prevalent and versatile cofactors in biological systems. One of the factors affecting the adaptability of these cofactors to a wide variety of different biological needs is the ease with which the redox state, and within each redox state, the electronic state of the iron, may be adjusted by porphyrin substituents and protein environment. During the next grant period we will concentrate on five projects: I. The structures, spectroscopic and redox properties of low-spin Fe(III) models of the cytochromes having large g max or Type I EPR spectra will be investigated by a wide array of spectroscopic techniques. At present we know that complexes with ligand plane dihedral angles as large as 30 degrees have Type II, while those with dihedral angles as small as 70 degrees have Type I EPR spectra. Detailed structural, spectroscopic and redox investigations of new complexes will allow us to determine how large the dihedral angles can be for Type II, and how small for Type I complexes. Electrochemical studies will allow investigation of the stabilities of the Fe(III) vs. Fe(II) axial ligand complexes, in order to see whether these complexes are indeed faithful models of the membrane-bound cytochromes having """"""""large g max"""""""" EPA signals in the oxidized state. II. Several carefully-chosen ferriheme proteins and their mutants will be investigated by magnetic spectroscopic techniques (in particular, pulsed EPA) to determine the orientation of the axial histidine (or exogenous imidazole) ligands, in order to (1) determine whether the exogenous ligand complexes are faithful models of the membrane-bound cytochromes having """"""""large g max"""""""" EPR signals in the oxidized state, and (2) to see if EPA signals can be assigned to particular hemes of complex multi-heme proteins. III. Models of the cytochromes, especially those having reduced heme rings and having axial or Type Ill EPA spectra suggestive of the (dxz,dyz)4 (dxy) ground state will be investigated by X-ray crystallography, magnetic spectroscopies and electrochemistry to determine whether they have this ground state, and if so, whether they have different redox reactivity than their (dxy)2(dxz,dyz)3 ground state counterparts. IV. The electronic ground state of model hemes having hydroperoxide as an axial ligand will be determined by pulsed EPA techniques, to determine whether they are (dxz,dyz)4(dxy)1 centers, and if so, V. H63M cytochrome b5, cytochrome P450cam, heme oxygenase and myoglobin having hydroperoxide as an axial ligand will be studied by pulsed EPA techniques to determine whether each is a (dxy)2(dxz,dyz)3 or (dxz,dyz)4(dxy)1 ground state center; if the latter, the mechanism of action of these enzymes will be better understood.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK031038-22
Application #
6705018
Study Section
Metallobiochemistry Study Section (BMT)
Program Officer
Sechi, Salvatore
Project Start
1982-05-01
Project End
2005-11-30
Budget Start
2003-12-01
Budget End
2004-11-30
Support Year
22
Fiscal Year
2004
Total Cost
$265,125
Indirect Cost
Name
University of Arizona
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721
Astashkin, Andrei V; Walker, F Ann (2013) Determination of the principal g-values of Type I or highly-anisotropic low spin (HALS) ferriheme centers in frozen solutions. J Magn Reson 231:15-21
Yang, Fei; Shokhireva, Tatiana K; Walker, F Ann (2011) Linear correlation between 1H and 13C chemical shifts of ferriheme proteins and model ferrihemes. Inorg Chem 50:1176-83
Hocking, Rosalie K; DeBeer George, Serena; Gross, Zeev et al. (2009) Fe L- and K-edge XAS of low-spin ferric corrole: bonding and reactivity relative to low-spin ferric porphyrin. Inorg Chem 48:1678-88
Shokhireva, Tatiana Kh; Smith, Kevin M; Berry, Robert E et al. (2007) Assignment of the ferriheme resonances of the high-spin forms of nitrophorins 1 and 4 by 1H NMR spectroscopy: comparison to structural data obtained from X-ray crystallography. Inorg Chem 46:170-8
Teschner, Thomas; Yatsunyk, Liliya; Schunemann, Volker et al. (2006) Models of the membrane-bound cytochromes: mossbauer spectra of crystalline low-spin ferriheme complexes having axial ligand plane dihedral angles ranging from 0 degree to 90 degrees. J Am Chem Soc 128:1379-89
Cai, Sheng; Shokhireva, Tatjana Kh; Lichtenberger, Dennis L et al. (2006) NMR and EPR studies of chloroiron(III) tetraphenyl-chlorin and its complexes with imidazoles and pyridines of widely differing basicities. Inorg Chem 45:3519-31
Cai, Sheng; Lichtenberger, Dennis L; Walker, F Ann (2005) NMR and EPR studies of the bis(pyridine) and bis(tert-butyl isocyanide) complexes of iron(III) octaethylchlorin. Inorg Chem 44:1890-903
Yatsunyk, Liliya A; Ogura, Hiroshi; Walker, F Ann (2005) Kinetics of ring inversion in strongly nonplanar iron(III) octaalkyltetraphenylporphyrinates. Inorg Chem 44:2867-81
Cai, Sheng; Belikova, Elena; Yatsunyk, Liliya A et al. (2005) Magnetic resonance and structural investigations of (monooxooctaethylchlorinato)iron(III) chloride and its bis(imidazole) complex. Inorg Chem 44:1882-9
Yatsunyk, Liliya A; Shokhirev, Nikolai V; Walker, F Ann (2005) Magnetic resonance spectroscopic investigations of the electronic ground and excited states in strongly nonplanar iron(III) dodecasubstituted porphyrins. Inorg Chem 44:2848-66

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