This project seeks to understand the molecular dynamics of the allosteric transition in hemoglobin, using spectroscopic probes of protein structure to investigate the change from low- to high-affinity states. These states control the hemoglobin function in healthy and diseased states. Their understanding is also critical for the development of hemoglobin-based blood substitutes. The spectroscopic techniques to be applied to hemoglobin are ultraviolet resonance Raman spectroscopy, and Fourier transform infrared spectroscopy. Both will be used in a time-resolved mode to generate spectra of transient states of the protein, and thereby provide structural mapping of the allosteric reaction coordinate.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM025158-17
Application #
2174391
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1978-06-01
Project End
1999-06-30
Budget Start
1995-07-01
Budget End
1996-06-30
Support Year
17
Fiscal Year
1995
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
Vaughn, Morgan B; Zhang, Jianyu; Spiro, Thomas G et al. (2018) Activity-Related Microsecond Dynamics Revealed by Temperature-Jump Förster Resonance Energy Transfer Measurements on Thermophilic Alcohol Dehydrogenase. J Am Chem Soc 140:900-903
Meadows, Corey W; Balakrishnan, Gurusamy; Kier, Brandon L et al. (2015) Temperature-Jump Fluorescence Provides Evidence for Fully Reversible Microsecond Dynamics in a Thermophilic Alcohol Dehydrogenase. J Am Chem Soc 137:10060-3
Balakrishnan, Gurusamy; Soldatova, Alexandra V; Reid, Philip J et al. (2014) Ultrafast charge transfer in nickel phthalocyanine probed by femtosecond Raman-induced Kerr effect spectroscopy. J Am Chem Soc 136:8746-54
Jones, Eric M; Monza, Emanuele; Balakrishnan, Gurusamy et al. (2014) Differential control of heme reactivity in alpha and beta subunits of hemoglobin: a combined Raman spectroscopic and computational study. J Am Chem Soc 136:10325-39
Jones, Eric M; Balakrishnan, Gurusamy; Squier, Thomas C et al. (2014) Distinguishing unfolding and functional conformational transitions of calmodulin using ultraviolet resonance Raman spectroscopy. Protein Sci 23:1094-101
Soldatova, Alexandra V; Ibrahim, Mohammed; Spiro, Thomas G (2013) Electronic structure and ligand vibrations in FeNO, CoNO, and FeOO porphyrin adducts. Inorg Chem 52:7478-86
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
Balakrishnan, Gurusamy; Hu, Ying; Spiro, Thomas G (2012) His26 protonation in cytochrome c triggers microsecond ?-sheet formation and heme exposure: implications for apoptosis. J Am Chem Soc 134:19061-9
Balakrishnan, Gurusamy; Jarzecki, Andrzej A; Wu, Qiang et al. (2012) Mode recognition in UV resonance Raman spectra of imidazole: histidine monitoring in proteins. J Phys Chem B 116:9387-95
Jones, Eric M; Balakrishnan, Gurusamy; Spiro, Thomas G (2012) Heme reactivity is uncoupled from quaternary structure in gel-encapsulated hemoglobin: a resonance Raman spectroscopic study. J Am Chem Soc 134:3461-71

Showing the most recent 10 out of 61 publications