As the four heme groups of the hemoglobin molecule become progressively saturated with ligands, such as oxygen or carbon monoxide, the ligand affinity of the unreacted heme groups increases. This necessitates a type of communication between these heme groups. It is the objective of this investigation to understand the molecular basis for this and the other related allosteric phenomena in hemoglobin. The functional properties of the different structural states of the molecule will be determined and the sequence of structural changes that accompany the saturation of the molecule with ligand explored. The structural transition in hemoglobin will be explored using carp hemoglobin as a model system since in this molecule the change in tertiary structure can be induced by variations of pH and organic phosphate concentration regardless of the state of liganding of the heme groups. The properties of antibody populations that react with single sites on heme protein antigens will be explored and the equilibrium and kinetic constants for their reactions with their specific antigens determined under a variety of conditions. Such site specific antibodies will be used as probes of structural changes at the surface of the hemoglobin molecule.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL012524-17
Application #
3334492
Study Section
Biophysics and Biophysical Chemistry A Study Section (BBCA)
Project Start
1977-05-01
Project End
1988-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
17
Fiscal Year
1986
Total Cost
Indirect Cost
Name
State University of New York at Buffalo
Department
Type
Schools of Medicine
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260
Friedman, J M; Campbell, B F; Noble, R W (1990) A possible new control mechanism suggested by resonance Raman spectra from a deep ocean fish hemoglobin. Biophys Chem 37:43-59
Noble, R W; DeYoung, A; Vitale, S et al. (1989) Spin equilibria in human methemoglobin: effects of bezafibrate and inositol hexaphosphate as measured by susceptometry and visible spectroscopy. Biochemistry 28:5288-92
Lin, M J; Noble, R W; Winterhalter, K H et al. (1988) Effects of ligand size on pH and organic phosphate-dependent affinity changes in carp hemoglobin as measured by isonitrile binding. Biochim Biophys Acta 954:73-81
Kwiatkowski, L D; Noble, R W (1987) Contribution of arginine (HC3) 141 alpha to the Bohr effect of the fourth binding step in the reaction of ligand with human hemoglobin. Proteins 2:72-7
Noble, R W; De Young, A; Vitale, S et al. (1987) Studies on the linkage between spin equilibria and protein structure in carp ferric hemoglobin. Eur J Biochem 168:563-7
Hirsch, R E; Noble, R W (1987) Intrinsic fluorescence of carp hemoglobin: a study of the R----T transition. Biochim Biophys Acta 914:213-9
Noble, R W; Kwiatkowski, L D; De Young, A et al. (1986) Functional properties of hemoglobins from deep-sea fish: correlations with depth distribution and presence of a swimbladder. Biochim Biophys Acta 870:552-63
Henry, E R; Rousseau, D L; Hopfield, J J et al. (1985) Spectroscopic studies of protein-heme interactions accompanying the allosteric transition in methemoglobins. Biochemistry 24:5907-18
Cerdonio, M; Morante, S; Torresani, D et al. (1985) Reexamination of the evidence for paramagnetism in oxy- and carbonmonoxyhemoglobins. Proc Natl Acad Sci U S A 82:102-3