Sulfur of methionine

Since in peptides and proteins alkyl halides at pH 2.8 react only with the sulfur of methionine (Gundlach et al, 1959b), this procedure permits specific chemical cleavage of methionyl peptide bonds. 

An analysis by Chakrabarti [21] of protein structures in the PDB showed that metal ions approach the sulfur of methionine at about 38(5)° from the perpendicular to the C-S-C group. This is similar to values in the range foimd, as just described, for smaU-molecule crystal structures in which the metal ion is presumed to interact with a sulfur lone-pair orbital [18]. It was also found that metal ions approach cysteine residues such that the M- -S-C-C torsion angle is 90° or 180°, and that the conformation of the cysteine side chain is generally affected by the metal ion. The metal ions that readily bind to sulfur in proteins are copper, iron, mercury, and zinc. The geometry of binding of metal ions to methionine or cysteine did not appear to depend on the identity of the individual metal. 

Reactions between the sulfur-containing amino acids cysteine and methionine (Fig. 2.18) and rufhenium(II) arene anticancer complexes are of much interest in view of the strong influence of sulfur amino acids on the intracellular chemistry of platinum drugs, their involvement in detoxification and resistance mechanisms [100]. We found [101] that [(ri -biphenyl)Ru(en)Cl][PF 5] reacts slowly with the thiol amino add L-cysteine in aqueous solution at 310 K, pH 2-5, and only to about 50% completion at a 1 2 mM ratio. Reactions appeared to involve aquation as the first step followed by initial formation of 1 1 adducts via substitution of water by S-bound or O-bound cysteine. Two dinuclear complexes were also detected as products from the reaction. In these reactions half or all of the chelated ethylene-diamine had been displaced and one or two bridging cysteines were present The unusual cluster species (biphenyl) Ru g was also formed espedaUy at higher cysteine concentrations. The reaction was suppressed in 50 mM triethylammo-nium acetate solution at pH > 5 or in 100 mM NaCl suggesting that thiols may not readily inactivate Ru(II)-en arene complexes in blood plasma or in cells. Similarly, reactions with the thioether sulfur of methionine appeared to be relatively weak. Only 27% of [(r -biphenyl)Ru(en)Cl][PF5] reacted with L-methionine (L-MetH) at an initial pH of 5.7 after 48 h at 310 K, and gave rise to only one adduct [(ri -biphenyl) Ru(en) (i-MetH -S)]. ... 

Synthesis of Sulfur Amino Acids. Of the many oxidation states of sulfur, only sulfite has been shown to be utilized by cell-free systems in the net synthesis of compounds with carbon-sulfur bonds, although mutant studies have indicated that more reduced forms can be incorporated. The formation of cysteinesulfinic acid from sulfite has been demonstrated in extracts of acetone-dried rabbit kidney it is possible that this reaction participates in the principal mechanism of sulfur incorporation. In many organisms that require preformed sulfur amino acids, cysteine may be formed from methionine. Only the sulfur of methionine is transferred to cysteine the carbon skeleton of cysteine is derived exclusively from serine. Transsulfuration appears to require the formation of homocysteine from methionine. Homocysteine and serine condense to form a thioether, cystathionine (V). Pyridoxal phosphate has been... 

The sulfur of both l- and D-methionine is oxidized in the intact animal. However, it does not appear that the sulfur of methionine is directly susceptible to oxidation, as neither methionine sulfoxide 0 0... 

The significance of these reactions for the metabolism of the sulfur of methionine is uncertain. It does not appear that they bulk very large quantitatively in the pathway of metabolism of methionine. 

The nucleophilic sulfur of methionine attacks the carbon of cyanogen bromide and displaces a bromide ion. 

Regarding the oxidation of methionine sulfur to taurine, the results of the experiments by Virtue and Doster-Virtue (134) with dogs have shown the existence of the oxidation reaction to be highly probable. The animals were first given a diet to deplete their taurine reserves a bile fistula operation was performed then ingestion of dZ-methiouine and cholic acid simultaneously was forced. This ingestion produces a decided increase in the quantity of excreted taurocholic acid. The absolute proof of the oxidation of sulfur of methionine to taurine has been furnished by Tarver and Schmidt... 

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