LIGAND REACTIVITY IN HEME PROTEINS

Project: Research project

Project Details

Description

It has been shown that ligands bind to hemoglobin (Hb) and myoglobin (Mb) in a sequence of microscopic steps. The overall binding process is both protein and ligand specific. How protein structure and dynamics control ligand binding in these model systems is a major focus of molecular biophysics. Several studies show that both ligand specificity (for 02 and CO) and protein structure specificity in the binding process originate at the level of ligand - iron bond formation. The bond forming step is most directly studied through geminate recombination (GR). GR has been studied using both cryogenic trapping techniques and fast time resolved spectroscopies at ambient temperatures. The cryogenic studies of GR provide detailed information about the kinetic barriers controlling bond formation. Extending the insights regarding GR from the cryogenic studies of biologically relevant temperatures is difficult because of the existence of temperature dependent motions that can influence the kinetic barriers. Ambient temperature studies reveal at least two ligand and structure dependent GR phases which has lead to a double potential energy well model for GR. How these two phases connect to the heavily studied single cryogenic geminate phase is unclear. We propose an extensive study of GR that will both link the two temperature regimes and expose how structure and structural dynamics control GR. We have preliminary results that indicate that the widely accepted. double well model is inadequate. We will also build on our findings that show that new optical pumping technique can be used: to modulate protein structure, to establish spectral correlations and to obtain detailed structure-function relationships. The objectives of this proposal will be pursued using time resolved spectroscopic tools including Raman and absorption. In addition a new rastering technique allows us to study structural dynamics at temperatures where sample recovery is slow.
StatusFinished
Effective start/end date9/30/928/31/95

Funding

  • National Institute of General Medical Sciences

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