Horikawa Tomonari, Hung Li Wei, Kim Heung Bok, Shaya David, Kim Chang Yub, Terwilliger Thomas C, Yamashita Eiki, Aoki Maho, Okada Ui, Murakami Satoshi
Department of Life Science and Technology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Acta Crystallogr F Struct Biol Commun. 2018 Nov 1;74(Pt 11):710-716. doi: 10.1107/S2053230X18013547. Epub 2018 Oct 16.
Burkholderia cenocepacia is an opportunistic pathogen that infects cystic fibrosis patients, causing pneumonia and septicemia. B. cenocepacia has intrinsic antibiotic resistance against monobactams, aminoglycosides, chloramphenicol and fluoroquinolones that is contributed by a homologue of BpeB, which is a member of the resistance-nodulation-cell division (RND)-type multidrug-efflux transporters. Here, the cloning, overexpression, purification, construct design for crystallization and preliminary X-ray diffraction analysis of this BpeB homologue from B. cenocepacia are reported. Two truncation variants were designed to remove possible disordered regions based on comparative sequence and structural analysis to salvage the wild-type protein, which failed to crystallize. The 17-residue carboxyl-terminal truncation yielded crystals that diffracted to 3.6 Å resolution. The efflux function measured using minimal inhibitory concentration assays indicated that the truncation decreased, but did not eliminate, the efflux activity of the transporter.
洋葱伯克霍尔德菌是一种机会致病菌,可感染囊性纤维化患者,引发肺炎和败血症。洋葱伯克霍尔德菌对单环β-内酰胺类抗生素、氨基糖苷类抗生素、氯霉素和氟喹诺酮类抗生素具有内在抗性,这是由BpeB的一个同源物导致的,BpeB是耐药-固氮-细胞分裂(RND)型多药外排转运蛋白家族的一员。本文报道了来自洋葱伯克霍尔德菌的这种BpeB同源物的克隆、过表达、纯化、用于结晶的构建体设计以及初步的X射线衍射分析。基于比较序列和结构分析设计了两个截短变体,以去除可能的无序区域,挽救未能结晶的野生型蛋白。17个残基的羧基末端截短产生了衍射分辨率达到3.6 Å的晶体。使用最低抑菌浓度测定法测量的外排功能表明,截短降低了但并未消除转运蛋白的外排活性。