Major Facilitator Superfamily transporters

Currently, five different molecular classes of mdr efflux pumps are known [5], While pumps of the the ATP-binding cassette (ABC) transporter superfamily are driven by ATP hydrolysis, the other four superfamilies called resistance-nodulation-division (RND), major facilitator superfamily (MFS), multidrug and toxic compound extrusion (MATE), and small multidrag resistance transporter (SMR) are driven by the proton-motive force across the cytoplasmic membrane. Usually a single pump protein is located within the cytoplasmic membrane. However, the RND-type pumps which are restricted to Gram-negative bacteria consist of two additional components, a periplasmic membrane fusion protein (MFP) which connects the efflux pump to an outer... 

An alternative to most of these mechanisms is the existence of efficient efflux systems, so that toxic concentrations of the drug are not achieved. There are three major families of proton-dependent multidrug efflux systems (1) the major facilitator superfamily, (2) the small multidrug resistance family, and (3) the resistance/nodulation/cell division family (Paulsen et al. 1996). It should be emphasized that several of these systems are involved not with antibiotic efflux but with, for example, acriflavine, chlorhexidine, and crystal violet. An attempt is made only to outline a few salient features of the resistance/nodulation/cell division family that mediates antibiotic efflux, and these are given in Table 3.3 (Nikaido 1996). They consist of a transporter, a linker, and an outer membrane channel. 

The Major Facilitator Superfamily (MFS) [95-97] is the largest secondary transporter family known in the genomes sequenced to date [98], These polytopic integral membrane proteins enable the transport of a wide range of solutes, including amino acids, sugars, ions, and toxins. Medically relevant members of the family include the bacterial efflux pumps associated with... 

The hexose-6-phosphate transporter UhpT protein also contains 12 transmembrane (TM) regions. Based on experimental data, Hall and Maloney [113] conclude that TM11 spans the membrane as an a-helix with approximately two-thirds of its surface lining a substrate translocation pathway. It is suggested that this feature is a general property of carrier proteins in the Major Facilitator Superfamily, and that, for this reason, residues in TM11 will serve to carry determinants of substrate selectivity [113]. 

AGA transporters found to be encoded in the production gene clusters of their producers are practically exclusively exporter-type systems. Otherwise they may belong to the large ABC drug exporter family or an ion-driven major facilitator superfamily (MFS with efflux-type transporter subfamilies). For instance. 

The lactose transporter is one member of the major facilitator superfamily (MFS) of transporters, which comprises 28 families. Almost all proteins in this superfamily have 12 transmembrane domains (the few exceptions have 14). The proteins share rela-... 

Wang DN. Three-dimensional crystallization of the Escherichia 68. coli glycerol-3-phosphate transporter a member of the major facilitator superfamily. Protein Sci. 2003 12 2748-2756. 

Goffeau A, et al. Multidrug-resistant transport proteins in yeast complete inventory and phylogenetic characterization of yeast 28. open reading frames with the major facilitator superfamily. Yeast 1997 13 43-54. 

Calabrese, D., Bille, J., and Sanglard, D. (2000) A novel multidrug efflux transporter gene of the major facilitator superfamily from Candida albicans FLIJI) conferring resistance to fluconazole. MicrobioJogy 146 (Pt 11), 2743-2754. 

Goffeau, A., Park, J., Paulsen, I.T., Jonniaux, J.-L., Dinh, T., Mordant, P., and Saier, M.H., Jr. 1997. Multidrug-resistant transport proteins in yeast Complete inventory and phylogenetic characterization of yeast open reading frames within the major facilitator superfamily. Yeast 13, 43-54. 

Gram-positive lactic acid bacteria possess several MDRs that excrete out of the cell a wide variety of mainly cationic lipophilic cytotoxic compotmds as well as many clinically relevant antibiotics. These MDRs are either proton/drug antiporters belonging to the major facilitator superfamily of secondary transporters or ATP-dependent primary transporters belonging to the ATP-binding cassette superfamily of transport proteins. 

HXT6 High-affinity glucose transporter of the major facilitator superfamily,... 

Elkins, C.A. and Savage, D.C. (2003) CbsT2 from Lactobacillus johnsonii 100-100 is a transport protein of the major facilitator superfamily that facOitates bile add antiporL J Mol Microbiol Biotechnol 6, 76-87. 

The ATP-binding cassette (ABC) superfamily and the major facilitator (MF) superfamily account for the majority of membrane transporters. 

The major facilitator (MF) superfamily of transporters (p. 457) isozymic forms of lactate dehydrogenase (p. 469)... 

Paulsen and colleagues (114, 115) determined the distribution of membrane transport proteins for all organisms with completely sequenced genomes and identified 81 distinct families. Two superfamilies, the ATP-binding cassette (ABC) and major facilitator... 

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