Cysteine into protein

Thiol groups enter some biologically important thiol compounds by the direct incorporation of cysteine itself. Most frequently this involves peptide bond formation. The incorporation of cysteine into proteins does not differ from any other amino acid involving activation as an amino acid adenylate, transfer to a specific transfer ribonucleic acid (t-RNA), and assembly by ribosomal enzymes as coded by messenger ribonucleic acid (m-RNA). It should be pointed out that cystine, the two-headed ... 

The rate of uptake of labelled cysteine into proteins has been extensively used as an indicator of the metabolic activity of tissues. S-L-cysteine administered to mice was found to be preferentially incorporated into growing hair follicles and claws. In other forms of epithelia the rate of... 

J. Stekol Dr. Krahl remarked about the availability of the component amino acids of GSH for incorporation into the protein. We also have experimented with S GSH and S cysteine incorporation in the intact growing animal maintained on diets of amino-acid mixtures. There was no difference in the extent of incorporation of S of GSH or S of cysteine into the protein of the rat. The results seem to indicate approximately equal availability of free cysteine or of cysteine of glutathione for incorporation into the protein of the intact animal. Another experiment was done by administering to intact animals S-p-bromobenzyl-benzoylgluta-thione. From the urine of these animals W-acetyl-S-p-bromobenzylcysteine was isolated. This, again, indicates hydrolysis of GSH to component amino acids in the intact rat. In a third experiment a C Mabeled mixture of the three component amino acids of GSH was administered to rats. The incorporation of cysteine into protein again was the same as when cysteine C alone was administered. 

The importance of the selenium-analog of cysteine, selenocysteine (Se-cysteine), HSeCH2CHNH2COOH, and its incorporation into protein via a ribosomal mechanism has earned it the label of the 21st amino acid.112 115 Assuming L configuration at the a carbon, Se-cysteine is represented by 49, R=H (Scheme 17). 

Metallothionein was first discovered in 1957 as a cadmium-binding cysteine-rich protein (481). Since then the metallothionein proteins (MTs) have become a superfamily characterized as low molecular weight (6-7 kDa) and cysteine rich (20 residues) polypeptides. Mammalian MTs can be divided into three subgroups, MT-I, MT-II, and MT-III (482, 483, 491). The biological functions of MTs include the sequestration and dispersal of metal ions, primarily in zinc and copper homeostasis, and regulation of the biosynthesis and activity of zinc metalloproteins. 

Fig. 4. A schematic representation of alternatively spliced Fas mRNA variants and the proteins they encode in normal PBMC. The upper three variants of FasA(4, 7), FasA(3, 4), and FasA(3, 4, 6) and the lower two variants of FasA(3, 4), and FasA(4, 6) were reported by Liu et al. (L6) and Papoff et al. (PI), respectively. The solid line indicates regions lacking in Fas mRNAs. The regions that are translated or not translated into proteins are indicated by boxes and broken lines, respectively. LR leader peptide CR, cysteine-rich subdomain TM, transmembrane domain ST, signal-transducing domain NR, negative regulation domain AL, altered amino acid region.

The thiazole ring is assembled on the 5-carbon backbone of 1-deoxyxylulose 5-phosphate, which is also an intermediate in the alternative biosynthetic pathway for terpenes (Fig. 22-2) and in synthesis of vitamin B6 (Fig. 25-21). In E. coli the sulfur atom of the thiazole comes from cysteine and the nitrogen from tyrosine.374 The same is true for chloroplasts,375 whereas in yeast glycine appears to donate the nitrogen.372 The thiamin biosynthetic operon of E. coli contains six genes,372a 376 one of which (ThiS) encodes a protein that serves as a sulfur carrier from cysteine into the thiazole.374 The C-terminal glycine is converted into a thiocarboxylate ... 

The unusual amino acid selenocysteine (a derivative of cysteine in which the sulfur atom is replaced by a selenium atom) is an essential component in a small number of proteins. These proteins occur in prokaryotes and eukaryotes ranging from E. coli to humans. In all cases, selenocysteine is incorporated into protein during translation in response to the codon UGA. This codon usually serves as a termination codon but occasionally, in some required but unknown context of bases, is used to specify selenocysteine instead. 

A possible function of this intracellular sulfur cycle is to buffer, i.e. to homeostatically regulate, the cysteine concentration of the cells. Irrespective of whether sulfate, cysteine, or sulfur dioxide is available as sulfur source, the intracellular sulfur cycle would allow a plant cell to use as much of these compounds as necessary for growth and development. At the same time, it would give a plant cell the possibility to maintain the cysteine pool at an appropriate concentration by emitting excess sulfur into the atmosphere. Thus, emission of hydrogen sulfide may take place when the influx of sulfur in the form of sulfate, cysteine, or sulfur dioxide exceeds the conversion of these sulfur sources into protein, glutathione, methionine, and other sulfur-containing components of the cell. 

Because of the strict stereochemical requirements, it is not easy to find optimal sites for the introduction of disulfide bonds into proteins. Introduction of disulfide bonds into T4 lysozyme has been engineered by theoretical calculations and computer modeling.4 7 The results obtained from the mutant lysozymes illustrate several points relevant to the use of disulfide bonds for improving protein stability.6 (i) Introduction of the cysteine(s) should minimize the disruption or loss of interactions that stabilize the native structure, (ii) The size of the loop formed by the crosslink should be as large as possible, (iii) The strain energy introduced by the disulfide bond should be kept as low as possible. For this purpose, a location within the flexible part of the molecule is desirable. 

Several plant proteins have been isolated that inhibit the metalloprotease carboxypeptidase A [205-217] (Table 7), notably potato carboxypeptidase inhibitor PCI [207-217] (Table 7). PCI is a small, cysteine-rich protein with a compact knotted structure determined by 3 disulphide links. The C-terminal region inserts into the active site of the carboxypeptidase. The C-terminal glycine is cleaved and remains trapped in the active site, this representing an example of suicide inactivation [207-216]. 

Cysteine is considered a nonessential nutrient because it can be synthesized from methionine via the transsulfuration pathway (Figs. 21-1 and 21-2). Production of cysteine is metabolically important because it serves as a source of sulfur for incorporation into proteins and detoxification reactions. A lack of cysteine needed for incorporation into the structural protein collagen may be responsible for the musculoskeletal abnormalities seen in patients with CBS deficiency. A major metabolic use of cysteine is in the production of glutathionine (y-glutamylcysteinylglycine), an important antioxidant. Another important pathway for cysteine metabolism is its oxidation to cysteinesulfinate, which serves as a precursor for taurine, an amino acid that stabilizes cell membranes in the brain. 

Excess copper is toxic to cells. On one hand, copper ions can avidly bind to biomolecules by ligand interaction with cysteines or by binding to histidine-rich regions. Copper ions could also be incorporated into proteins instead of zinc or other metal ions during biosynthesis. On the other hand, copper ions can form radicals by a Fenton-type reaction as shown in Eq. (1) ... 

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