Crystal Structures of the Mycobacterium tuberculosis Rv3066 Transcriptional Regulator
The Mycobacterium tuberculosis Rv3066 protein is a proposed transcriptional regulator controlling the expression of the multi-drug efflux pump Mmr (Rv3065). We determined the crystal structures of both the apo and ethidium-bound forms of this regulator at 2.3 Å resolution. The structures suggest that Rv3066 is an all ?-helical two-domain protein similar to other members of the TetR-family. The N-terminal domains contain a conserved helix-turn-helix DNA binding motif with significant conformational variations, suggesting conformational flexibility. The C-terminal domains display a multi-drug binding cavity containing anionic charged and aromatic amino acids necessary for the binding of cationic drugs. In vitro studies reveal that the dimeric Rv3066 regulator binds to a 14-bp palindromic inverted repeat (IR) sequence at the promoter region to repress the expression of Mmr.