Abstract

Studies of molecular structure and dynamics in heme proteins will be carried out using laser-excited resonance Raman spectroscopy. A theoretical and computational framework for extracting structural information from the spectra will be implemented using recently developed porphyrin force fields and molecular graphics. Protein-heme interactions in cytochrome c peroxidase will be investigated systematically with site- directed mutants. The dynamics of quaternary structure change in hemoglobin will be explored wit ultraviolet resonance Raman spectroscopy. Electron transfer and conformational coupling in cytochrome oxidase will be investigated with transient absorption and Raman techniques. These studies are expected to help uncover the molecular mechanisms whereby oxygen metabolism is linked to biological function through the motions of proteins.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM033576-20
Application #
3283462
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1979-04-01
Project End
1994-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
20
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Princeton University
Department
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544

  Publications

Spiro, Thomas G; Soldatova, Alexandra V; Balakrishnan, Gurusamy (2013) CO, NO and O2 as Vibrational Probes of Heme Protein Interactions. Coord Chem Rev 257:511-527
Kabil, Omer; Weeks, Colin L; Carballal, Sebastian et al. (2011) Reversible heme-dependent regulation of human cystathionine ýý-synthase by a flavoprotein oxidoreductase. Biochemistry 50:8261-3
Ibrahim, Mohammed; Derbyshire, Emily R; Marletta, Michael A et al. (2010) Probing soluble guanylate cyclase activation by CO and YC-1 using resonance Raman spectroscopy. Biochemistry 49:3815-23
Soldatova, Alexandra V; Ibrahim, Mohammed; Olson, John S et al. (2010) New light on NO bonding in Fe(III) heme proteins from resonance Raman spectroscopy and DFT modeling. J Am Chem Soc 132:4614-25
Ibrahim, Mohammed; Derbyshire, Emily R; Soldatova, Alexandra V et al. (2010) Soluble guanylate cyclase is activated differently by excess NO and by YC-1: resonance Raman spectroscopic evidence. Biochemistry 49:4864-71
Weeks, Colin L; Singh, Sangita; Madzelan, Peter et al. (2009) Heme regulation of human cystathionine beta-synthase activity: insights from fluorescence and Raman spectroscopy. J Am Chem Soc 131:12809-16
Singh, Sangita; Madzelan, Peter; Stasser, Jay et al. (2009) Modulation of the heme electronic structure and cystathionine beta-synthase activity by second coordination sphere ligands: The role of heme ligand switching in redox regulation. J Inorg Biochem 103:689-97
Derbyshire, Emily R; Gunn, Alexander; Ibrahim, Mohammed et al. (2008) Characterization of two different five-coordinate soluble guanylate cyclase ferrous-nitrosyl complexes. Biochemistry 47:3892-9
Xu, Changliang; Ibrahim, Mohammed; Spiro, Thomas G (2008) DFT analysis of axial and equatorial effects on heme-CO vibrational modes: applications to CooA and H-NOX heme sensor proteins. Biochemistry 47:2379-87
Spiro, Thomas (2008) A twist on heme signaling. ACS Chem Biol 3:673-5

Showing the most recent 10 out of 53 publications