Glutathione, function structure

Glutaric acid, structure of, 753 Glutathione, function of. 668 prostaglandin biosynthesis and, 1070... 

In paper [49] various models of the active site of metal-containing enzyme glutathion-transferase having structures with five and six coordinated ions Mn + and Fe + are explored. In both cases it is assumed, that the respective metal ion is in its HS state. It essentially facilitates calculation since such a ground state can be reasonably modelled by a single-configuration (HER) wave function. Structural studies of the Jahn-Teller effect in TMCs by the ab initio CC methods are performed in [50,51]. 

SHEEHAN D, MEADE G, FOLEY V M and DOWD 0 A (2001) Structure, function and evolution of glutathione transferases implications for classification of non-mammalian members of an ancient enzyme superfamily , Biochem J, 360 1-16. 

The Na/K ATPase has been extensively purified and characterized, and consists of a catalytic a subunit of around 95 kDa and a glycoprotein 0 subunit of approximately 45 kDa (Skou, 1992). The functional transporter exists as a dimer with each monomer consisting of an a and /3 subunit. Hiatt aal. (1984) have su ested that the non-catalytic jS subunit may be involved in the cottect insertion of the a subunit into the lipid bilayer and, therefore, it is conceivable that a modification of the 0 subunit structure may be reflected by changes in the catalytic activity of the a subunit. Therefore, in studies involving the manipulation of tissue glutathione levels, alterations of intracellular redox state may have an effect on substrate binding at an extracellular site on this ion-translocating protein. 

If cellular redox state, determined by the glutathione status of the heart, plays a role in the modulation of ion transporter activity in cardiac tissue, it is important to identify possible mechanisms by which these effects are mediated. Protein S-,thiolation is a process that was originally used to describe the formation of adducts of proteins with low molecular thiols such as glutathione (Miller etal., 1990). In view of the significant alterations of cardiac glutathione status (GSH and GSSG) and ion-transporter activity during oxidant stress, the process of S-thiolation may be responsible for modifications of protein structure and function. 

Figure 4.14 Diagrammatic representation of (a) oxy-radical>mediated S-thioiation and (b) thiol/disulphide-initiated S-thiolation of protein suiphydryl groups. Under both circumstances mixed disuiphides are formed between glutathione and protein thiois iocated on the ion-translocator protein resulting in an alteration of protein structure and function. Both of these mechanisms are completely reversible by the addition of a suitabie reducing agent, such as reduced glutathione, returning the protein to its native form.

Bousset, L., Belrhali, H., Melki, R., and Morera, S. (2001b). Crystal structures of the yeast prion Ure2p functional region in complex with glutathione and related compounds. Biochemistry 40, 13564-13573. 

Coenzymes complement the catalytic action of the amino-acid functional groups. They are bound to apoenzymes (apoproteins) either covalently or non-covalently. It is interesting to note that non-covalently-bound coenzymes are polyanions at neutral pH as exemplified by the structures of glutathione (GSH) [17] and thiamine pyrophosphate [18]. Shinkai and Kunitake (1976b, 1977a) demonstrated the efficient binding of glutathione and coenzyme A (a polyphosphate) to cationic micelles and cationic polysoaps. Thus, the combina- ... 

In lipoic acid (6), an intramolecular disulfide bond functions as a redox-active structure. As a result of reduction, it is converted into the corresponding dithiol. As a prosthetic group, lipoic acid is usually covalently bound to a lysine residue (R) of the enzyme, and it is then referred to as lipoamide. Lipoamide is mainly involved in oxidative decarboxylation of 2-0X0 acids (see p. 134). The peptide coenzyme glutathione is a similar disulfide/ dithiol system (not shown see p. 284). 

If a metabolite is pharmacologically active or structural alert (i.e., contains a reactive functional group, glutathione conjugates) then it should be considered for monitoring in toxicological and/or clinical studies. 

Recently, active recombinant a-LTX has been generated using bacteria in which both thioredoxin reductase and glutathione reductase are inactivated to improve the formation of disulphide bonds in expressed proteins (Li et al. 2005). The toxin is expressed as a fusion with glutathione-S-transferase (GST), which is used for affinity purification of the recombinant toxin and can be subsequently removed by selective proteolysis. Considering the relative ease of generating recombinant proteins in bacteria, this approach will facilitate structure-function studies of a-LTX. 

The G-6-PD is a large structure with many genetic variants perhaps more than any other human protein (59-62). It is an almost ubiquitous cytosolic enzyme which catalyzes the first step in the hexose monophosphate pathway (62). Its most essential function is to produce the NADPH required to maintain the concentration of reduced glutathione (GSH) in the face of oxidative stress. The GSH together with catalase and glutathione peroxidase represent the defence against hydrogen peroxide, and this is particularly true in red blood cells. 

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