Redox-active amino acids

Volume 258. Redox-Active Amino Acids in Biology Edited by Judith P. Klinman... 

The realization of the widespread occurrence of amino acid radicals in enzyme catalysis is recent and has been documented in several reviews (52-61). Among the catalytically essential redox-active amino acids glycyl [e.g., anaerobic class III ribonucleotide reductase (62) and pyruvate formate lyase (63-65)], tryptophanyl [e.g., cytochrome peroxidase (66-68)], cysteinyl [class I and II ribonucleotide reductase (60)], tyrosyl [e.g., class I ribonucleotide reductase (69-71), photosystem II (72, 73), prostaglandin H synthase (74-78)], and modified tyrosyl [e.g., cytochrome c oxidase (79, 80), galactose oxidase (81), glyoxal oxidase (82)] are the most prevalent. The redox potentials of these protein residues are well within the realm of those achievable by biological oxidants. These redox enzymes have emerged as a distinct class of proteins of considerable interest and research activity. 

REDOX-ACTIVE AMINO ACIDS Affinity chromatography of NADA... 

AMINE OXIDASE REDOX-ACTIVE AMINO ACIDS... 

ELECTROSTRICTION DIETHYL PYROCARBONATE Diferric-tyrosyl radical cofactor, REDOX-ACTIVE AMINO ACIDS... 

REDOX-ACTIVE AMINO ACIDS DOPAMINE j8-MONOOXYGENASE... 

ENZYME KINETIC EQUATIONS REDOX-ACTIVE AMINO ACIDS TOPAQUINONE REDOX POTENTIAL Redox reactions,... 

ACTIN ASSEMBLY KINETICS MICROTUBULE ASSEMBLY KINETICS Triglyceride synthesis kinetics (hepatic), LIRID TRACER KINETICS 2,4,5-Trihydroxyphenylalanine quinone, REDOX-ACTIVE AMINO ACIDS TRIMOLECULAR MOLECUARITY ORDER... 

Bollinger JM, Tong WH, Ravi N, Huynh BH, Edmondson DE, Stubbe J. Redox-active amino acids in biology. 1995, 258, 278. 

Fig. 9. Redox-active amino acid residues related to tyrosine, (a) Tyrosine, the redox center in ribonucleotide reductase, prostaglandin H synthase, and the photosynthetic oxygen evolving complex, (b) 2,4,5-Trihydroxyphenylalanine, the redox cofactor of the quinoprotein amine oxidase, (c) Tyrosine-cysteine (Tyr-Cys), the redox cofactor of galactose oxidase.

Seyedsayamdost, M. R., Yee, C. S., Reece, S. Y., et al. (2006) pH rate profiles of FnY356-R2s (n = 2, 3,4) in Escherichia coli ribonucleotide reductase Evidence that Y-356 is a redox-active amino acid along the radical propagation pathway. Journal of the American Chemical Society, 128(5), 1562-1568. 

Aside from general caveats that apply to many in vitro models, there is one concern specific to research on AGs and cisplatin. Their mechanisms of toxicity involve the formation of ROS and are therefore sensitive to the antioxidant capacity of the incubation medium. This parameter is rarely controlled and different standard media contain varying amounts of redox-active amino acids, glutathione, or other compounds. Even the common pH indicator phenol red is an important contributor to the total antioxidant capacity of cell and tissue culture media [97]. Thus, the antioxidative capacity of the incubation media may differ from the endolymph and comparable media need to be used to compare therapeutic efficiencies. The concern applies not only to studies of ototoxic mechanisms of these drugs but perhaps even more also to attempts to identify protective treatments which most frequently include therapeutics with antioxidant properties. 

Redox-active amino acids are now recognized to play important roles in many biological electron-transfer reactions. In 1988, Bridgette Barry and Gerry Babcock" used EPR spectroscopy to demonstrate the involvement of an isotope-labeled radical in the water-splitting reaction in photosystem II of... 

Redox-active amino acids in water splitting)... 

Fig. 20. Structure of photosynthetic electron carriers and electron-transfer proteins (A) ATP, NAD and NADP (B) quinones (C) redox-active amino acids tyrosine and histidine (D) cytochromes and f (E) iron-sulfur proteins and (F) the copper protein plastocyanin.

R3. BA Barry (1993) The roie of redox-active amino acids in the photosynthetic water-oxidizing compiex. Photochem Photobiol 57 179-188... 

Genetic methods provide a powerful approach to the biosynthetic introduction of redox groups [including cysteine residues as well as unnatural redox active amino acids (79)] into proteins. As an example, a disulfide bridge inserted across the active site of T4 lysozyme has been used to create a redox mechanism for regulating enzyme activity (SO). Oxidation of the cysteines to form the disulfide closes the active site region, whereas reduction exposes the active site and restores catalytic activity. 

Whittaker, J. W. Spectroscopic Studies of Galactose Oxidase. In Methods in Enzymology, Redox-Active Amino Acids in Biology, Klinman, J. P., Ed., Academic Press San Diego, CA, 1995 Vol. 258, pp 262-277. 

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