Cysteinyl residue loss

Table 9.10 Preventive actions against cysteinyl residue loss.

Two missense mutations (C282Y and H63D) in the HFE gene have been identified in hereditary hemochromatosis. The substitution of a tyrosyl residue for a cysteinyl residue at position 282 results in the loss of formation of a... 

We have shown previously that carboxymethylation of the active center cysteinyl residues of LADH also inactivates the enzyme and renders the zinc atoms less stable (17), If enzyme labeled with Zn in acetate buffer is carboxymethylated and then dialyzed, only the unlabeled zinc atoms are lost. In this instance, the two Zn labeled atoms remaining do interact with OP and, therefore, are "exposed (Table III). Thus, although carboxymethylation completely inactivates the enzyme, this is not because of the loss of its catalytically essential zinc atoms. Rather, the zincs which are lost upon carboxymethylation appear to be those most critical in maintenance of the quaternary structure as shown earlier in ultracentrifugal experiments (17). 

Zhang H, Amunugama H, Ney S, Cooper N, Hollenberg PF (2011) Mechanism-based inactivation of human cytochrome P450 2B6 by clopidogrel leads to both covalent modification of cysteinyl residue 475 and loss of heme. Mol Pharmacol 80 839-847... 

D-Xylosidase from Bacillus pumilus has been shown to contain one intramolecular disulphide bridge and four L-cysteinyl residues per monomer (mol. wt. 6.0 X 10 ). Under native conditions, one L-cysteinyl residue per polypeptide chain reacted with 5,5 -dithiobis(2-nitrobenzoic acid) or 4-chloro-mercuribenzoate resulting in complete loss of enzymic activity. Reductive treatment with dithiothreitol completely reversed this loss. Kinetic analysis of the inactivation reaction pointed to a saturation effect, occurring when the concentration of the — SH-directed reagent was increased. A reaction model, which included prior association of the reagent with the enzyme, was proposed. 

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