The Major Facilitator Superfamily

In the Organophosphate Phosphate Antiporter (OPA) family (2. A. 1.4), most members preferentially catalyze substrate substrate antiport, but they can also catalyze substrate H symport, and some preferentially seem to use a symport rather than an antiport mechanism. Also, in the Nitrate/ Nitrite Porter (NNP) family (2.A. 1.8), members of similar sequence can catalyze either uptake, efflux, or NO j NO exchange. Finally, members of the Organocation Transporter (OCT) family in animals (2.A.1.19) appear to be mechanistically promiscuous, catalyzing substrate uptake, export, exchange, and/or uniport. Sometimes the mechanism and substrate H stoichiometry depends on 

Group LAB Non-LAB Firmicutes Actinobacteria Gram (-) bacteria Archaea 

MFS carriers are usually about 400 amino acyl residues (aa) long and have 12 transmembrane a-helical spanners (TMSs) with two homologous repeat units, each of six TMSs. They are found ubiquitously in bacteria, archaea, and eukaryotes. Over 20,000 sequenced MFS members are available for sequence analysis, and x-ray structures have been reported for several of them (Law et al. 2008). Some evidence suggests that the basic 6-TMS repeat unit arose by duplication of a primordial three TMS encoding genetic element and that MFS carriers arose from simple two TMS ion channels (Hvorup and Saier 2002 Vastermark et al. 2014). 

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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]. 

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,... 

A second lipid flippase that moves lyso-PE across the inner membrane was recently discovered (E.M. Harvat, 2005). This protein belongs to the major facilitator superfamily... 

Ward A, Hoyle C, Palmer S, O Reilly J, Griffith J, Pos M, Morrison S, Poolman B, Gwynne M, Henderson P (2001). Prokaryote multidrug efflux proteins of the major facilitator superfamily Amplified expression, purification and characterization. J. Mol. Biotechnol. 3 193-200. 

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. 

Hvomp, R.N. and Saier, M.H., Jr. (2002) Sequence similarity between the channel-forming domains of voltage-gated ion channel proteins and the C-terminal domains of secondary carriers of the major facilitator superfamily. Microbiology 148,3760-3762. 

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