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The TetA(K) tetracycline/H(+) antiporter from Staphylococcus aureus: mutagenesis and functional analysis of motif C. 2000

S L Ginn, and M H Brown, and R A Skurray
School of Biological Sciences, University of Sydney, Sydney, New South Wales 2006, Australia.

Conserved motif C, identified within members of the major facilitator superfamily (MFS) of transport proteins that mediate drug export, was examined in the tetracycline resistance efflux protein TetA(K) from Staphylococcus aureus; motif C is contained within transmembrane segment 5. Using site-directed mutagenesis, the importance of the conserved glycine (G151, G155, G159, and G160) and proline (P156) residues within this motif was investigated. Over 40 individual amino acid replacements were introduced; however, only alanine and serine substitutions for glycine at G151, G155, and G160 were found to retain significant levels of tetracycline resistance and transport activity in cells expressing mutant proteins. Notably, P156 and G159 appear to be crucial, as amino acid replacements at these positions either significantly reduced or abolished tetracycline/H(+) activity. The highly conserved nature of motif C and its distribution throughout drug exporters imply that the residues of motif C play a similar role in all MFS proteins that function as antiporters.

UI MeSH Term Description Entries
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D001426 Bacterial Proteins Proteins found in any species of bacterium. Bacterial Gene Products,Bacterial Gene Proteins,Gene Products, Bacterial,Bacterial Gene Product,Bacterial Gene Protein,Bacterial Protein,Gene Product, Bacterial,Gene Protein, Bacterial,Gene Proteins, Bacterial,Protein, Bacterial,Proteins, Bacterial
D013211 Staphylococcus aureus Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.
D013752 Tetracycline A naphthacene antibiotic that inhibits AMINO ACYL TRNA binding during protein synthesis. 4-Epitetracycline,Achromycin,Achromycin V,Hostacyclin,Sustamycin,Tetrabid,Tetracycline Hydrochloride,Tetracycline Monohydrochloride,Topicycline,4 Epitetracycline
D013753 Tetracycline Resistance Nonsusceptibility of bacteria to the action of TETRACYCLINE which inhibits aminoacyl-tRNA binding to the 30S ribosomal subunit during protein synthesis.
D016297 Mutagenesis, Site-Directed Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion. Mutagenesis, Oligonucleotide-Directed,Mutagenesis, Site-Specific,Oligonucleotide-Directed Mutagenesis,Site-Directed Mutagenesis,Site-Specific Mutagenesis,Mutageneses, Oligonucleotide-Directed,Mutageneses, Site-Directed,Mutageneses, Site-Specific,Mutagenesis, Oligonucleotide Directed,Mutagenesis, Site Directed,Mutagenesis, Site Specific,Oligonucleotide Directed Mutagenesis,Oligonucleotide-Directed Mutageneses,Site Directed Mutagenesis,Site Specific Mutagenesis,Site-Directed Mutageneses,Site-Specific Mutageneses
D017920 Antiporters Membrane transporters that co-transport two or more dissimilar molecules in the opposite direction across a membrane. Usually the transport of one ion or molecule is against its electrochemical gradient and is "powered" by the movement of another ion or molecule with its electrochemical gradient. Anion Exchange Proteins,Antiporter,Cation Exchange Proteins,Anion Exchangers (Proteins),Cation Exchangers (Proteins),Exchange Proteins, Anion,Exchange Proteins, Cation
D020816 Amino Acid Motifs Three-dimensional protein structural elements that are composed of a combination of secondary structures. They include HELIX-LOOP-HELIX MOTIFS and ZINC FINGERS. Motifs are typically the most conserved regions of PROTEIN DOMAINS and are critical for domain function. However, the same motif may occur in proteins or enzymes with different functions. AA Motifs,Motifs, Amino Acid,Protein Motifs,Protein Structure, Supersecondary,Supersecondary Protein Structure,AA Motif,Amino Acid Motif,Motif, AA,Motif, Amino Acid,Motif, Protein,Motifs, AA,Motifs, Protein,Protein Motif,Protein Structures, Supersecondary,Supersecondary Protein Structures

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