The Construction and Analysis of the Multidrug Resistance Transporter Knowledge-Base

Abstract

Multidrug resistance (MDR) proteins serve as transporters for chemical compounds, small molecules like antibiotics in almost all species from bacteria to higher eukaryote. They provide the resistance against antibiotics and agrichemicals for the cells like cancer, fungi and parasite, etc. Therefore, the research on MDR protein is essential and important in medical, agricultural and scientific fields. Five transporter protein families are known to contain the MDR members as follows. ABC (ATPBinding Cassette superfamily), MFS (Major-Facilitator Superfamily), SMR (Small Multidrug Resistance family), RND (Resistance-Nodulation-cell Division family) and MATE (Multidrug and Toxic compound Extrusion family). The ABC and MFS consist of some subfamilies. Only the ABC transporter is driven by ATP hydrolysis energy, and other four families are driven by proton motive force. It was reported that more than 90% of MDR genes are composed of ABC and MFS genes in completely sequenced bacteria genomes [1]. In general, the relationship of the transporter and its substrate is highly specific, but MDRs are known to be transporters which have broad spectrums of drugs and chemical compounds. Therefore, the MDRs are not specific but poly-specific rather than non-specific transporters. Many substrates have been found and used in experiments for elucidating the mechanism and property of MDRs. The spectrum of each MDR family is known to be somewhat distinct, but the relationship to the structural and physicochemical properties of substrates has not been well established. In this study, we collected the substrates from the literature and tried to retrieve structural and physicochemical properties that are representative of each substrate of MDRs and to define relationships between MDR families and their substrates.