Reorganization energy cofactors

In principle it should be possible to determine the reorganization energy simply by examining the temperature dependence of the reaction to determine the activation energy, without the need to replace natural redox centers with exotic cofactors, or mutational changes to modulate midpoint potentials. However, this method is fraught with traps for the unwary. First, it may be more appropriate to use the semi-classical version of the... 

The electronic coupling has been calculated for each of the flavin electron transfer complexes described in this chapter and is described below, with the exceptions of CPR, TMADH and PDR. For these three proteins, the two redox cofactors are in direct van der Waals contact, either between the C-7 and C-8 methyl groups of two flavins (CPR), or between the flavin C-8 methyl and a cysteinyl sulfur ligand to the iron-sulfur center (TMADH and PDR). In these cases the coupling between the redox centers should be maximal and the electron transfer rates should depend only on the driving foree and reorganization energy for the electron transfer proeesses. 

The ability to control redox potentials and reorganization energies in proteins comes at a price ET partners buried within insulating polypeptides cannot come into close contact to exchange electrons. The essential electronic interaction between redox cofactors must be mediated by the polypeptide matrix. Extensive experimental and theoretical efforts have been aimed at elucidating the factors that regulate distant electronic couplings between redox sites in proteins. ... 

Variations in X can have enormous effects on electron-transfer rates. Some of the possible variations are apparent from inspection of Equation (6.20). First, Xo decreases with increasing reactant size. Second, the dependence of the reaction rate on separation distance attributable to Xo occurs via the l/d term. Third, Xo decreases markedly as the solvent polarity decreases. For nonpolar solvents, Ds — Dap = 1.5 to 4.0. It is significant to note that protein interiors are estimated to have 0 — 4, whereas, Dg = 78 for water. An important conclusion is that metalloproteins that contain buried redox cofactors need not experience large outer-sphere reorganization energies. 

Energetic constraints on the medium reorganization energy. E is a local property, which is essentially determined by the interaction of cofactors and their ions with the amino acid residues in their vicinity. 

The apparent absence of a strong dependence of the medium reorganization energy on specific cofactor structural elements is also reflected in another property of the cofactor-protein interaction, the difference between the protein solvation free energy of the reduced and oxidized cofactor species (aaG°soi (reduced-oxidized)). aaG°jq represents the contribution of the protein-cofactor interaction to the value of E fin situ), and hence to -AG°et-Values for aaG°sq (Kcal/mole) can be estimated from ... 

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