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Mutant form C 115 H of C lostridium sporogenes methionine γ‐lyase efficiently cleaves S ‐Alk(en)yl‐ l ‐cysteine sulfoxides to antibacterial thiosulfinates
Author(s) -
Kulikova Vitalia V.,
Anufrieva Natalya V.,
Revtovich Svetlana V.,
Chernov Alexander S.,
Telegin Georgii B.,
Morozova Elena A.,
Demidkina Tatyana V.
Publication year - 2016
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.1562
Subject(s) - cysteine , chemistry , enzyme , biochemistry , clostridium sporogenes , lyase , mutant , methionine , enzyme assay , bacteria , stereochemistry , clostridium , biology , amino acid , gene , genetics
Pyridoxal 5'‐phosphate‐dependent methionine γ‐lyase (MGL) catalyzes the β‐elimination reaction of S‐alk(en)yl‐ l ‐cysteine sulfoxides to thiosulfinates, which possess antimicrobial activity. Partial inactivation of the enzyme in the course of the reaction occurs due to oxidation of active site cysteine 115 conserved in bacterial MGLs. In this work, the C115H mutant form of Clostridium sporogenes MGL was prepared and the steady‐state kinetic parameters of the enzyme were determined. The substitution results in an increase in the catalytic efficiency of the mutant form towards S‐substituted l ‐cysteine sulfoxides compared to the wild type enzyme. We used a sulfoxide/enzyme system to generate antibacterial activity in situ . Two‐component systems composed of the mutant enzyme and three S‐substituted l ‐cysteine sulfoxides were demonstrated to be effective against Gram‐positive and Gram‐negative bacteria and three clinical isolates from mice. © 2016 IUBMB Life, 68(10):830–835, 2016