The general long-term goal of this program involving heme proteins is to attain a molecular understanding of the mechanisms by which the associated polypeptides interact with a common heme group to produce the remarkable functional diversity which characterizes this class of proteins. The essential strategy is to apply powerful spectroscopic probes such as resonance Raman and time-resolved resonance Raman to the native and systematically manipulated proteins in order to reveal the structural and dynamic interactions which regulate heme reactivity. Recently developed methodology now allows several fundamentally important questions to be approached. For example, isotope sensitivity of molecular vibrations is exploited to selectively probe individual sites in functioning native hemoglobin and in rational site specific mutants to reveal a better understanding of allosteric cooperativity. Also, application of novel rapid-mixing techniques, coupled with available site-specific mutants will facilitate a thorough investigation of the active site structure of previously inaccessible catalytic intermediates of important oxidative heme enzymes such as cytochrome P450 and various peroxidases.
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