Institute of Biotechnology, Czech Academy of Sciences, v.v.i., BIOCEV, Průmyslová 595, 252 50 Vestec, Czech Republic.
Acta Crystallogr F Struct Biol Commun. 2023 Jul 1;79(Pt 7):180-192. doi: 10.1107/S2053230X23005381. Epub 2023 Jul 5.
The resistance of the emerging human pathogen Stenotrophomonas maltophilia to tetracycline antibiotics mainly depends on multidrug efflux pumps and ribosomal protection enzymes. However, the genomes of several strains of this Gram-negative bacterium code for a FAD-dependent monooxygenase (SmTetX) homologous to tetracycline destructases. This protein was recombinantly produced and its structure and function were investigated. Activity assays using SmTetX showed its ability to modify oxytetracycline with a catalytic rate comparable to those of other destructases. SmTetX shares its fold with the tetracycline destructase TetX from Bacteroides thetaiotaomicron; however, its active site possesses an aromatic region that is unique in this enzyme family. A docking study confirmed tetracycline and its analogues to be the preferred binders amongst various classes of antibiotics.
新兴人类病原体嗜麦芽寡养单胞菌对四环素类抗生素的耐药性主要取决于多药外排泵和核糖体保护酶。然而，这种革兰氏阴性菌的几个菌株的基因组编码一种 FAD 依赖性单加氧酶（SmTetX），与四环素破坏酶同源。该蛋白被重组表达，并对其结构和功能进行了研究。使用 SmTetX 的活性测定表明，它能够修饰土霉素，其催化速率可与其他破坏酶相媲美。SmTetX 与拟杆菌属的四环素破坏酶 TetX 具有相同的折叠结构；然而，其活性位点具有该酶家族特有的芳香族区域。对接研究证实，四环素及其类似物是各种抗生素中首选的结合物。
