Protein control of true, gated, and coupled electron transfer reactions.
Electron transfer (ET) through and between proteins is a fundamental biological process. The rates of ET depend upon the thermodynamic driving force, the reorganization energy, and the degree of electronic coupling between the reactant and product states. The analysis of protein ET reactions is complicated by the fact that non-ET processes might influence the observed ET rate in kinetically complex biological systems. This Account describes studies of the methylamine dehydrogenase-amicyanin-cytochrome c-551i protein ET complex that have revealed the influence of several features of the protein structure on the magnitudes of the physical parameters for true ET reactions and how they dictate the kinetic mechanisms of non-ET processes that sometimes influence protein ET reactions. Kinetic and thermodynamic studies, coupled with structural information and biochemical data, are necessary to fully describe the ET reactions of proteins. Site-directed mutagenesis can be used to elucidate specific structure-function relationships. When mutations selectively alter the electronic coupling, reorganization energy, or driving force for the ET reaction, it becomes possible to use the parameters of the ET process to determine how specific amino acid residues and other features of the protein structure influence the ET rates. When mutations alter the kinetic mechanism for ET, one can determine the mechanisms by which non-ET processes, such as protein conformational changes or proton transfers, control the rates of ET reactions and how specific amino acid residues and certain features of the protein structure influence these non-ET reactions. A complete description of the mechanism of regulation of biological ET reactions enhances our understanding of metabolism, respiration, and photosynthesis at the molecular level. Such information has important medical relevance. Defective protein ET leads to production of the reactive oxygen species and free radicals that are associated with aging and many disease states. Defective ET within the respiratory chain also causes certain mitochondrial myopathies. An understanding of the mechanisms of regulation of protein ET is also of practical value because it provides a logical basis for the design of applications utilizing redox enzymes, such as enzyme-based electrode sensors and fuel cells.
Davidson
Victor L
VL
Department of Biochemistry, The University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA. vdavidson@biochem.umsmed.edu
D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003300:Copper / Q000737:chemistry; D003574:Cytochrome c Group / Q000737:chemistry / Q000378:metabolism*; D004579:Electron Transport; D004583:Electrons; D007700:Kinetics; D016297:Mutagenesis, Site-Directed; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000737:chemistry / Q000378:metabolism*; D010231:Paracoccus denitrificans / Q000201:enzymology / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D001426:Bacterial Proteins; D003574:Cytochrome c Group; D014867:Water; D003300:Copper; C017167:cytochrome C(551); C021567:methylamine dehydrogenase; D000587:Oxidoreductases Acting on CH-NH Group Donors