Structure of the Tet repressor-tetracycline complex and regulation of antibiotic resistance.
The most frequently occurring resistance of Gram-negative bacteria against tetracyclines is triggered by drug recognition of the Tet repressor. This causes dissociation of the repressor-operator DNA complex and enables expression of the resistance protein TetA, which is responsible for active efflux of tetracycline. The 2.5 angstrom resolution crystal structure of the homodimeric Tet repressor complexed with tetracycline-magnesium reveals detailed drug recognition. The orientation of the operator-binding helix-turn-helix motifs of the repressor is inverted in comparison with other DNA binding proteins. The repressor-drug complex is unable to interact with DNA because the separation of the DNA binding motifs is 5 angstroms wider than usually observed.
Hinrichs
W
W
Institut für Kristallographie, Freie Universität Berlin, Germany.
Kisker
C
C
Düvel
M
M
Müller
A
A
Tovar
K
K
Hillen
W
W
Saenger
W
W
D017920:Antiporters / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D004269:DNA, Bacterial / Q000378:metabolism; D018257:Helix-Loop-Helix Motifs; D006860:Hydrogen Bonding; D008274:Magnesium / Q000737:chemistry; D008958:Models, Molecular; D009154:Mutation; D009875:Operator Regions, Genetic; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013752:Tetracycline / Q000737:chemistry* / Q000378:metabolism; D013753:Tetracycline Resistance / Q000235:genetics
D017920:Antiporters; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D012097:Repressor Proteins; C034811:tetracycline resistance-encoding transposon repressor protein; D013752:Tetracycline; D008274:Magnesium