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The key players in Klebsiella pneumoniae homocysteine biosynthesis: enzymatic characterization of recombinant cystathionine γ-synthase and cystathionine β-lyaseстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 15 апреля 2026 г.
- Авторы: Morozova Elena, Anufrieva Natalya, Kulikova Vitalia, Sidorova Alena, Revtovich Svetlana, Solyev Pavel
- Журнал: Bioorganic Chemistry
- Том: 169
- Год издания: 2026
- Издательство: Academic Press
- Местоположение издательства: United States
- Номер статьи: 109420
- DOI: 10.1016/j.bioorg.2025.109420
- Аннотация: Amino acid biosynthesis pathways are essential for cell growth as they supply the fundamental building blocks for protein synthesis. Such pathways in pathogenic cells can serve as an excellent target in the development of antimicrobial drugs. Our study examined key enzymes of the bacterial transulfuration pathway, cystathionine γ-synthase (kCGS) and cystathionine β-lyase (kCBL) from Klebsiella pneumoniae, an opportunistic microorganism belonging to the group of ESKAPE pathogens that causes nosocomial infections and causes significant clinical problems for its high frequency and diversity of antimicrobial resistance genes. The recombinant enzymes were expressed in E. coli, purified and characterized. The kCGS catalyzes the γ-replacement reaction at the first stage of the transsulfuration pathway, the succinyl group of O-succinyl-L-homoserine (OSH) being replaced by the thiol of L-cysteine to form L-cystathionine with the efficiency kcat/Km L-OSH = 1.8 × 105 M−1 s−1. The catalytic efficiency of the second stage enzyme kCBL in the reaction of β-elimination of L-cystathionine is 5.8 × 104 M−1 s−1. In addition to its natural function, the kCGS exhibits O-succinylhomoserine sulfhydrylase activity by catalyzing the γ-substitution of the succinyl group of O-succinyl-L-homoserine for sulfide and, thus, it can furnish L-homocysteine synthesis via direct sulfhydrylation pathway. Analysis of the K. pneumoniae genome allowed us to assume that the bacterium uses the transsulfuration pathway to synthesize L-homocysteine, and therefore kCGS and kCBL can be used as potential targets to create selective inhibitors of these enzymes.
- Добавил в систему: Сольев Павел Николаевич