Post-translational protein redox

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. 

Clearly, the control of gene expression at the transcriptional level is a key regulatory mechanism controlling carotenogenesis in vivo. However, post-transcriptional regulation of carotenoid biosynthesis enzymes has been found in chromoplasts of the daffodil. The enzymes phytoene synthase (PSY) and phytoene desaturase (PDS) are inactive in the soluble fraction of the plastid, but are active when membrane-bound (Al-Babili et al, 1996 Schledz et al, 1996). The presence of inactive proteins indicates that a post-translational regulation mechanism is present and is linked to the redox state of the membrane-bound electron acceptors. In addition, substrate specificity of the P- and e-lycopene cyclases may control the proportions of the p, P and P, e carotenoids in plants (Cunningham et al, 1996). 

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. 

In relatively recent times, a number of biologically novel structures that function as cofactors in redox reactions, some of them as agents of hydride transfer, have been discovered to be present in enzyme or other protein structures. They are often covalently bound and are formed in post-translational reactions from the side-chains of normal, genetically encoded amino-acid residues. The structures are shown in Fig. 4.3, taken from Mure s excellent review [2]. The important chemical functionality of these coenzymes is the quinone ring, an ortho-quinone in most cases, both a para-quinone and an ortho-quinone in TPQ. 

Bao, J., Sack, M. (2010) Protein deacetylation by sirtuins delineating a post-translational regulatory program responsive to nutrient and redox stressors. Cellular and... 

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. 

---