新型 FOX-8 AmpCβ-内酰胺酶的特性研究表明，位于 R2 环的单个突变 Phe313Leu 影响头孢他啶的水解。
Characterization of the new AmpC β-lactamase FOX-8 reveals a single mutation, Phe313Leu, located in the R2 loop that affects ceftazidime hydrolysis.
机构信息
Servicio de Microbiología-INIBIC, Complejo Hospitalario Universitario A Coruña, A Coruña, Spain.
出版信息
Antimicrob Agents Chemother. 2013 Oct;57(10):5158-61. doi: 10.1128/AAC.00818-13. Epub 2013 Jul 22.
Abstract
A novel class C β-lactamase (FOX-8) was isolated from a clinical strain of Escherichia coli. The FOX-8 enzyme possessed a unique substitution (Phe313Leu) compared to FOX-3. Isogenic E. coli strains carrying FOX-8 showed an 8-fold reduction in resistance to ceftazidime relative to FOX-3. In a kinetic analysis, FOX-8 displayed a 33-fold reduction in kcat/Km for ceftazidime compared to FOX-3. In the FOX family of β-lactamases, the Phe313 residue located in the R2 loop affects ceftazidime hydrolysis and alters the phenotype of E. coli strains carrying this variant.
摘要
一种新型的 C 类β-内酰胺酶（FOX-8）从一株临床分离的大肠杆菌中分离得到。与 FOX-3 相比，FOX-8 酶具有一个独特的取代（Phe313Leu）。携带 FOX-8 的同基因大肠杆菌菌株对头孢他啶的耐药性降低了 8 倍，而 FOX-3 则降低了 8 倍。在动力学分析中，FOX-8 对头孢他啶的 kcat/Km 降低了 33 倍，而 FOX-3 则降低了 33 倍。在 FOX 家族的β-内酰胺酶中，位于 R2 环的 Phe313 残基影响头孢他啶的水解，并改变携带该变异体的大肠杆菌菌株的表型。
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2
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10
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