Structural and functional studies will be carried out in order to provide a molecular-level understanding of the role of heme proteins in fundamental physiological processes, including respiration metabolism, and the regulation of cellular responses. Resonance Raman spectroscopy will be applied as a structural monitor of the heme group, and of its interaction with proteins and with exogenous ligands, including especially the newly discovered signaling molecule NO. Computer modeling with a high quality force field will be employed in order to extract maximum information from the spectra.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM033576-28
Application #
2444578
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1979-04-01
Project End
1998-12-31
Budget Start
1997-07-01
Budget End
1998-12-31
Support Year
28
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Princeton University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
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

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