Post-translational protein redox modifications

Further in vivo experiments demonstrated that AS exhibits a unique nitrosation signature which differs from that of DEA-NO inasmuch as substantial amounts of a mercury-resistant nitroso species are generated in the heart, whereas Y-nitrosothiols are the major reaction products in plasma. These data are consistent with the notion that the generation of nitroxyl in vivo gives rise to formation of nitrosative post-translational protein modifications in the form of either S- or Wnitroso products, depending on the redox environment. 

The introduction and implementation of heteronuclear-based multidimensional techniques have revolutionized the protein NMR field. Large proteins (> 100 residues) are now amenable to detailed NMR studies and structure determination. These techniques, however, necessarily require a scheme by which and isotopes can be incorporated into the protein to yield a uniformly labeled sample. Additional complications, such as extensive covalent post-translational modifications, can seriously limit the ability to efficiently and cost effectively express a protein in isotope enriched media - the c-type cytochromes are an example of such a limitation. In the absence of an effective labeling protocol, one must therefore rely on more traditional proton homonuclear NMR methods. These include two-dimensional (1) and, more recently, three-dimensional H experiments (2,3). Cytochrome c has become a paradigm for protein folding and electron transfer studies because of its stability, solubility and ease of preparation. As a result, several high-resolution X-ray crystal structure models for c-type cytochromes, in both redox states, have emerged. Although only subtle structural differences between redox states have been observed in these... 

Latterly, much interest has focussed on redox cell signalling, which involves the post-translational modification of signal transduction proteins by reactive oxygen and nitrogen species. Therefore, the purpose of this review is twofold firstly, to review the nature of reaction of biologically relevant oxidants and secondly, yet most importantly, to consolidate our knowledge of the chemical modifications to biomolecules. 

Both cofactors are involved in respiratory electron transfer systems (Figure 5.19), for example, in most redox reactions of the citric acid (Krebs) cycle. NAD is most often involved in degradation (catabolism) of sugars, fats, proteins and ethanol, while NADP is involved mainly in biosynthetic (anabolic) reactions, such as synthesis ofmacromolecules, fatty acids and cholesterol. Dinucleotides, in addition of their activities in redox reactions, participate in post-translational modifications of some proteins and other reactions. 

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