This proposal seeks to elucidate the structure and function of iron-containing enzymes involved in oxygen activation. Moreover, it is proposed to study a variety of Fe(IV) containing synthetic compounds that mimic structural and electronic features of the active sites of the enzymes under study. Further, it is proposed to study the Mossbauer spectra of proteins in overexpressing E. coli cells. The experimental techniques employed are Mossbauer spectroscopy, Electron paramagnetic resonance (EPR) and SQUID magnetometry. It is also proposed to study high-valent Fe(IV) sites of proteins and model complexes with density functional theory. ? ? (1) Studies of the diiron proteins methane monooxygenase, ribonucleotide reductase, delta9 desaturase and phenolhydroxylase will be continued. ? (2) This research will be complemented by studies of model complexes to gain insight into the electronic structure of the active sites of the enzymes. ? (3) Whole-cell studies of iron containing proteins overexpressed in E. coli will be continued. ? (4) The Mossbauer and EPR spectra of compound I of cytochrome P450 isolated from a thermophilic bacterium will be studied. ? (5) Mossbauer and EPR studies of four non-heme iron proteins suspected to pass in their catalytic cycles through an Fe(IV)=O intermediate will be performed. ? (6) Iron(IV) sites occurring in enzymes and model complexes will be investigated with density functional theory. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
9R01EB001475-28
Application #
6607791
Study Section
Metallobiochemistry Study Section (BMT)
Program Officer
Mclaughlin, Alan Charles
Project Start
1990-05-01
Project End
2008-04-30
Budget Start
2003-05-01
Budget End
2004-04-30
Support Year
28
Fiscal Year
2003
Total Cost
$340,053
Indirect Cost
Name
Carnegie-Mellon University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
052184116
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Stoian, Sebastian A; Xue, Genqiang; Bominaar, Emile L et al. (2014) Spectroscopic and theoretical investigation of a complex with an [O?Fe(IV)-O-Fe(IV)?O] core related to methane monooxygenase intermediate Q. J Am Chem Soc 136:1545-58
Li, Feifei; Van Heuvelen, Katherine M; Meier, Katlyn K et al. (2013) Sc3+-triggered oxoiron(IV) formation from O2 and its non-heme iron(II) precursor via a Sc3+-peroxo-Fe3+ intermediate. J Am Chem Soc 135:10198-201
McDonald, Aidan R; Guo, Yisong; Vu, Van V et al. (2012) A Mononuclear Carboxylate-Rich Oxoiron(IV) Complex: a Structural and Functional Mimic of TauD Intermediate 'J' Chem Sci 3:1680-1693
Li, Feifei; Chakrabarti, Mrinmoy; Dong, Yanhong et al. (2012) Structural, EPR, and Mössbauer characterization of (?-alkoxo)(?-carboxylato)diiron(II,III) model complexes for the active sites of mixed-valent diiron enzymes. Inorg Chem 51:2917-29
Van Heuvelen, Katherine M; Fiedler, Adam T; Shan, Xiaopeng et al. (2012) One-electron oxidation of an oxoiron(IV) complex to form an [O?FeV?NR]+ center. Proc Natl Acad Sci U S A 109:11933-8
Fleischhacker, Angela S; Stubna, Audria; Hsueh, Kuang-Lung et al. (2012) Characterization of the [2Fe-2S] cluster of Escherichia coli transcription factor IscR. Biochemistry 51:4453-62
Cranswick, Matthew A; Meier, Katlyn K; Shan, Xiaopeng et al. (2012) Protonation of a peroxodiiron(III) complex and conversion to a diiron(III/IV) intermediate: implications for proton-assisted O-O bond cleavage in nonheme diiron enzymes. Inorg Chem 51:10417-26
McDonald, Aidan R; Van Heuvelen, Katherine M; Guo, Yisong et al. (2012) Characterization of a thiolato iron(III) Peroxy dianion complex. Angew Chem Int Ed Engl 51:9132-6
Chakrabarti, Mrinmoy; Munck, Eckard; Bominaar, Emile L (2011) Density functional theory study of an all ferrous 4Fe-4S cluster. Inorg Chem 50:4322-6
Schwalbe, Matthias; Dogutan, Dilek K; Stoian, Sebastian A et al. (2011) Xanthene-modified and hangman iron corroles. Inorg Chem 50:1368-77

Showing the most recent 10 out of 54 publications