Common Features in Substrates of Multidrug Resistance Transporters

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 chemicals for the cells like cancer, fungi and parasite, etc. Therefore, the research on MDR proteins is essential and important in medical, agricultural and scientific fields. Five transporter families are known to contain MDR members as follows. ABC (ATP-binding 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 transporter consists of some subfamilies, such as pgp, mrp and pdr. The ABC transporter is driven by ATP hydrolysis energy, and the other four families are driven by proton/sodium motive force. It was reported that more than 90% of MDR genes are composed of ABC and MFS genes in completely sequenced bacteria genomes [4]. In general, the relationship of the transporter and its substrate is highly specific, but MDRs are known to be transporters that have broad spectrums of drugs and chemical compounds. Thus, MDRs are poly-specific rather than nonspecific transporters [5]. Many substrates have been found and used in experiments for characterizing properties 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. Previously, we collected chemical compound structures for substrates of MDR proteins from the published literature and tried to retrieve structural and physicochemical properties [2], They were represented by 67 kinds of the KEGG atom types [1]. In this study, we classified these collected chemical compound substrates and extracted common sub-graphs of them by using Vzyme [3] in order to detect putative recognition sites in chemical compound substrates by the MDR protein.