细菌多药外排系统及其探究方法进展.doc

细菌多药外排系统及其探究方法进展 　 【摘要】; 位于细菌细胞膜上的多药外排泵可将多种结构无关药物排出，本文综述了细菌主要外排泵包括初级和次级转运系统的分子生物学特征及外排蛋白结构与药物识别和转运上的关系；同时总结了对外排蛋白进行结构与功能关系研究的主要的方法，包括定点诱变、螺旋空间排列和结晶等。 毕业论文 【关键词】; 细菌 外排泵 多药耐药 毕业论文 ; Introduction 毕业论文 ; The problem of drug resistance is a main obstacle in the struggle between human being and infectious diseases. One of the most important bacterial resistant mechanisms is the multidrug efflux pumps situated on the membranes, which can be classified into two major types based on the energy source: primary transport system, such as ATP?binding cassette (ABC) transporter superfamily utilizes the energy produced by ATP hydrolysis to efflux diverse compounds; while secondary transport system pumps different substrates via the proton motive force (PMF) providing by transmembrane electrochemical proton gradient (ΔμH+) or the sodium motive force supplying by ion gradients (ΔμNa+). Despite the totally different evolutionary trait and energy sources, both can transport a broad spectrum of structurally unrelated substrates. ; To date, due to the highly hydrophobic nature, the crystallization of the structure on most of the membrane transporters is yet to be cracked down, albeit recently, a few have been partially crystallized. Therefore, the most important analysis approach is still protein engineering methods involving site?directed mutagenesis and chemical modification. And currently there have developed some improvements on these methods. 毕业论文 ; Bacterial multidrug efflux pump systems 毕业论文 ; ATP?binding cassette (ABC) transporter 毕业论文 ; To date, LmrA is the only well?characterised bacterial?origin ABC transporter, which is encoded by chromosomally located lmrA gene in Lactococcus lactis. In general, active ABC proteins demand minimal two transmembrane domains (TMDs) and two ABC units (nucleotide?binding domain, NBD). The former usually consists of six transmembrane segments (α?helices); the latter, a 200～250 amino acids, contains three conserved motifs Wal