Quantum chemistry calculations of spectral parameters would be compared with experimental spectroscopy (NMR, IR and Mossbauer) on the active site structures of heme proteins, with the aim to probe heme-ligand bond angles and heme ruffling, particularly in the paramagnetic states. The long term goals are (1) to understand specificity in small molecule binding to heme proteins, and (2) to validate quantum chemical methods for computing NMR shifts, other spectroscopic quantities and energetics in metallo-proteins. Studies of heme proteins and model systems are proposed, including DFT calculations of paramagnetic shifts and Mossbauer splittings. A variety of NMR measurements will be used to refine the structures of myoglobin, carbonmonoxy-myglobin, cytochrome c from the ferricytochrome c-cytochrome c peroxidase complex. Finally, with the help of the understandng of spectroscopy heme systems, and with Dr. Oldfield's refined structures of the proteins, the energetics of binding of small molecules to hemes will be studied, which he hypothesizes are dominated by hydrogen bonding interactions in the cavity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB000271-25
Application #
6682866
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Program Officer
Mclaughlin, Alan Charles
Project Start
1992-04-01
Project End
2005-03-31
Budget Start
2003-04-01
Budget End
2005-03-31
Support Year
25
Fiscal Year
2003
Total Cost
$295,610
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
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Zhang, Yong; Sun, Haihong; Oldfield, Eric (2005) Solid-state NMR fermi contact and dipolar shifts in organometallic complexes and metalloporphyrins. J Am Chem Soc 127:3652-3
Oldfield, Eric (2005) Quantum chemical studies of protein structure. Philos Trans R Soc Lond B Biol Sci 360:1347-61
Zhang, Yong; Mukherjee, Sujoy; Oldfield, Eric (2005) (67)Zn NMR chemical shifts and electric field gradients in zinc complexes: a quantum chemical investigation. J Am Chem Soc 127:2370-1
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Wouters, Johan; Oudjama, Yamina; Ghosh, Subhash et al. (2003) Structure and mechanism of action of isopentenylpyrophosphate-dimethylallylpyrophosphate isomerase. J Am Chem Soc 125:3198-9
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