LIGAND REACTIVITY IN HEMEPROTEINS

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 date9/30/928/31/97

ASJC

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)