Quinone-protein interactions

Favreau LV, Pickett CB. 1993. Transcriptional regulation of the rat NAD(P)H quinone reductase gene. Characterization of a DNA-protein interaction at the antioxidant responsive element and induction by 12-O-tetradecoylphorbol 13-acetate. J Biol Chem 268 19875-19881. 

R3. JP Allen, G Feher, TO Yeates, H Komiya and DC Rees (1988) Structure of the reaction centerfrom Rhodobacter sphaeroldes R-26 Protein-cofactor (quinones andPe ) interactions. Proc Nat Acad Sci, USA 85 8487-8491... 

The functional diversity of flavoproteins results from the broad range of redox potentials that are accessible to the flavin cofactors, as well as their ability to switch between one or two electron redox chemistry. In solution, flavins are found in equilibrium between the oxidized, reduced and the semi-quinone radical forms, and have a redox potential of about —210 mV (versus the normal hydrogen electrode) at neutral pH. However, in the protein-bound form, the redox equilibrium can be shifted and the redox potential may span up to 600 mV (Massey 2000). This arises from the fact that flavin-protein interactions may engage a number of non-covalent interactions such as 7i-stacking, hydrophobic effects, hydrogen bonding and electrostatic interactions, which will ultimately determine the flavin redox potential. 

While electronic transitions of the pigments and the quinones can be used to trace the immediate involvement of these cofactors in the reactions, only very limited information is available on the dynamic nature of the cofactor-protein interactions, on protolytic reactions in the quinone environment, and on local protein conformational changes, all possibly contributing to the stabilization of the charged radical states in the RC. 

Cosolvents ana Surfactants Many nonvolatile polar substances cannot be dissolved at moderate temperatures in nonpolar fluids such as CO9. Cosolvents (also called entrainers, modifiers, moderators) such as alcohols and acetone have been added to fluids to raise the solvent strength. The addition of only 2 mol % of the complexing agent tri-/i-butyl phosphate (TBP) to CO9 increases the solubility ofnydro-quinone by a factor of 250 due to Lewis acid-base interactions. Veiy recently, surfac tants have been used to form reverse micelles, microemulsions, and polymeric latexes in SCFs including CO9. These organized molecular assemblies can dissolve hydrophilic solutes and ionic species such as amino acids and even proteins. Examples of surfactant tails which interact favorably with CO9 include fluoroethers, fluoroacrylates, fluoroalkanes, propylene oxides, and siloxanes. 

In the ci positional state, fast electron transfer from the Rieske protein to cytochrome Ci will he facilitated hy the close interaction and by the hydrogen bond between His 161 of the Rieske protein and a propionate group of heme Ci, but the Rieske cluster is far away from the quinone binding site. 

After the second electron transfer from semiquinone to heme 6l (step 4), the interaction between the Rieske cluster and the resulting quinone is weakened so that the reduced Rieske protein can now occupy the preferred ci positional state (E), which allows rapid electron transfer from the Rieske cluster to heme Ci (step 5). 

Bolton, J. L. Turnipseed, S. B. Thompson, J. A. Influence of quinone methide reactivity on the alkylation of thiol and amino groups in proteins studies utilizing amino acid and peptide models. Chem.-Biol. Interact. 1997, 107, 185-200. 

Thompson, D. C. Perera, K. London, R. Spontaneous hydrolysis of 4-trifluoromethyl-phenol to a quinone methide and subsequent protein alkylation. Chem.-Biol. Interact. 2000, 126, 1-14. 

Glutathione is also implicated in the removal of toxic metabolites from the analgesic paracetamol (USA acetaminophen). Oxidative metabolism of paracetamol produces an A-hydroxy derivative, and this readily loses water to generate a reactive and toxic quinone imine, which interacts with proteins to cause cell damage. 

Some regulatory mechanisms have been revealed for the TPHs, such as activation by phosphorylation-dependent interaction with 14-3-3 proteins (71,72). Catecholamines are also reported to be inhibitors of TPH (73). l-DOPA and L-DOPA-quinone derivatives, but not the end product serotonin, have also been shown to be inhibitors of TPH activity (see Martinez et al. 2001 (74) for the physiological and pharmacological implications of the inhibitory effects by catechol derivatives). 

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