Protein radiation biochemistry

Radiation Biochemistry of Proteins and Amino Acids. Up to the levels of 500 krads the changes in pigment properties of heme proteins are similar to those caused by oxidation or reduction. Changes in the proteins, in addition to deamination and loss of —SH groups, indicate a partial de-naturation similar to that induced by hydrogen ions. This results in some enhancement of reactivity of the heme portion (2). 

Simic M, Dizdaroglu M (1985) Formation of radiation-induced cross-links between thymine and tyrosine Possible model for cross-linking of DNA and proteins by ionizing radiation. Biochemistry 24 234-236... 

The alkylperoxyl radical can be expected to react with sulfur amino acids by mechanisms similar to those for HOO- and HO-. Reactions of the hydroxyl and hydroperoxyl radicals have been more extensively studied because of their importance in radiation biochemistry. Thus, for cysteine, glutathione, and sulfhydryl proteins,... 

Studies in radiation biochemistry have shown that there is some localization of free radical damage to enzymes and proteins at their sulfur amino acids. In proteins irradiated in solution cysteine, cystine and methionine arc some of the most labile amino acids. Radiation in the dry state allows electron spin resonance measurements and Gordy (1958) has shown the localization of unpaired electrons at sulfur in amino acids and proteins. As described previously in this article, in the damage to cytochrome c by linolenate peroxidation, cystine and methionine are among the most labile amino acids. If damage is localized at a sulfhydryl site on a protein, immediate molecular repair is possible by a sulfur interchange of the unpaired electron,... 

Gajewski E, Fuciarelli AF, Dizdaroglu M (1988) Structure of hydroxyl radical-induced DNA-protein crosslinks in calf thymus nucleohistone in vitro. Int J Radiat Biol 54 445-459 Gajewski E, Rao G, Nackerdien Z, Dizdaroglu M (1990) Modification of DNA bases in mammalian chromatin by radiation-generated free radicals. Biochemistry 29 7876-7882 Garner A, Scholes G (1985) Mechanism of the photohydration of pyrimidines a flash photolysis study. Photochem Photobiol 41 259-265... 

The Intention of this volume is to give a flavour of the types of problems in biochemistry that theoretical calculations can solve at present, and to illustrate the tremendous predictive power these approaches possess. With these aspects in mind, I have tried to gather some of the leading scientists in the field of theoretical/computational biochemistry and let them present their work. You will hence find a wide range of computational approaches, from classical MD and Monte Carlo methods, via semi-empirical and DFT approaches on isolated model systems, to Car-Parrinello QM-MD and novel hybrid QM/MM studies. The systems investigated also cover a broad range from membrane-bound proteins to various types of enzymatic reactions as well as inhibitor studies, cofactor properties, solvent effects, transcription and radiation damage to DNA. 

Boiteux, S., Gajewski, E., Laval, J., and Dizdaroglu, M. (1992) Substrate specificity of the Escherichia coli Fpg protein (formamidopyrimidine-DNA glycosylase) excision of purine lesions in DNA produced by ionizing radiation or photosensitization. Biochemistry, 31, 106-110. 

A chapter in an earlier compilation [1] bringing together fundamentals and applications of radiation chemistry illustrated applications to biochemistry and radiobiology. That chapter mainly described studies of redox processes in proteins and biomolecules. It therefore seemed appropriate to focus instead a major part of the present review on free radicals derived from xenobiotic molecules, especially drugs of interest in cancer therapy. 

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