Woolridge D P, Vazquez-Laslop N, Markham P N, Chevalier M S, Gerner E W, Neyfakh A A
Departments of Biochemistry and Radiation Oncology, The University of Arizona Health Science Center, Tucson, Arizona 85724, USA.
J Biol Chem. 1997 Apr 4;272(14):8864-6. doi: 10.1074/jbc.272.14.8864.
Multidrug transporters pump structurally dissimilar toxic molecules out of cells. It is not known, however, if detoxification is the primary physiological function of these transporters. The chromosomal organization of the gene encoding the Bacillus subtilis multidrug transporter Blt suggests a specific function for this protein; it forms a single operon with another gene, bltD, whose protein product is identified here as a spermine/spermidine acetyltransferase, an enzyme catalyzing a key step in spermidine degradation. Overexpression of the Blt transporter in B. subtilis leads not only to the multidrug-resistance phenotype but also to the efflux of large amounts of spermidine into the medium; this efflux is supressed by an inhibitor of Blt, reserpine. Taken together, these results strongly suggest that the natural function of the Blt transporter is the efflux of spermidine, whereas multiple drugs may be recognized by Blt merely opportunistically.
多药转运蛋白将结构不同的有毒分子泵出细胞。然而，这些转运蛋白的解毒作用是否为其主要生理功能尚不清楚。编码枯草芽孢杆菌多药转运蛋白Blt的基因的染色体组织表明该蛋白具有特定功能；它与另一个基因bltD形成一个单一操纵子，此处鉴定出其蛋白产物为精胺/亚精胺乙酰转移酶，该酶催化亚精胺降解的关键步骤。在枯草芽孢杆菌中过表达Blt转运蛋白不仅导致多药耐药表型，还导致大量亚精胺外流到培养基中；这种外流被Blt抑制剂利血平抑制。综上所述，这些结果强烈表明Blt转运蛋白的天然功能是亚精胺外流，而多种药物可能只是被Blt偶然识别。
