Acinetobacter baumannii is a multidrug-resistant pathogen that has become one of the most challenging pathogens in global healthcare. Several antibiotic-resistant genes, including catB8, have been identified in the A. baumannii genome. CatB8 protein, one of the chloramphenicol acetyltransferases (Cats), is encoded by the catB8 gene. Cats can convert chloramphenicol (chl) to 3-acetyl-chl, leading to bacterial resistance to chl. Here, we present the high-resolution cocrystal structure of CatB8 with chl. The structure that we resolved showed that each monomer of CatB8 binds to four chl molecules, while its homologous protein only binds to one chl molecule. One of the newly discovered chl binding site overlaps with the site of another substrate, acetyl-CoA. Through structure-based biochemical analyses, we identified key residues for chl recruiting and acetylation of chl in CatB8. Our work is of significant importance for understanding the drug resistance of A. baumannii and the effectiveness of antibiotic treatment.

中文翻译：

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鲍曼不动杆菌氯霉素乙酰转移酶 CatB8 的氯霉素结合位点

鲍曼不动杆菌是一种多重耐药病原体，已成为全球医疗保健中最具挑战性的病原体之一。鲍曼不动杆菌基因组中已鉴定出多种抗生素抗性基因，包括catB8。CatB8 蛋白是氯霉素乙酰转移酶 (Cats) 之一，由catB8基因编码。猫可以将氯霉素 (chl) 转化为 3-乙酰基-chl，从而导致细菌对 Chl 产生耐药性。在这里，我们展示了 CatB8 与 Chl 的高分辨率共晶结构。我们解析的结构表明，CatB8的每个单体与四个chl分子结合，而其同源蛋白仅与一个chl分子结合。新发现的叶绿素结合位点之一与另一个底物乙酰辅酶A的位点重叠。通过基于结构的生化分析，我们确定了 CatB8 中叶绿素募集和叶绿素乙酰化的关键残基。我们的工作对于了解鲍曼不动杆菌的耐药性和抗生素治疗的有效性具有重要意义。