3qpl

G106W mutant of EthR from Mycobacterium tuberculosis

spinqualitylabelsall models 3qpl, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3qpl is a 1 chain structure with sequence from "bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 3o8g, 3o8h, 3g1m, 3q0u, 3q0v, 3q0w, 1u9n Gene: ethR, etaR, MT3970, Rv3855 ("Bacillus tuberculosis" (Zopf 1883) Klein 1884) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ETHR_MYCTU] Involved in the repression of the monooxygenase EthA which is responsible of the formation of the active metabolite of ethionamide (ETH). Publication Abstract from PubMed Ethionamide is an antituberculous drug for the treatment of multidrug-resistant Mycobacterium tuberculosis. This antibiotic requires activation by the monooxygenase EthA to exert its activity. Production of EthA is controlled by the transcriptional repressor EthR, a member of the TetR family. The sensitivity of M. tuberculosis to ethionamide can be artificially enhanced using synthetic ligands of EthR that allosterically inactivate its DNA-binding activity. Comparison of several structures of EthR co-crystallized with various ligands suggested that the structural reorganization of EthR resulting in its inactivation is controlled by a limited portion of the ligand-binding-pocket. In silico simulation predicted that mutation G106W may mimic ligands. X-ray crystallography of variant G106W indeed revealed a protein structurally similar to ligand-bound EthR. Surface plasmon resonance experiments established that this variant is unable to bind DNA, while thermal shift studies demonstrated that mutation G106W stabilizes EthR as strongly as ligands. Proton NMR of the methyl regions showed a lesser contribution of exchange broadening upon ligand binding, and the same quenched dynamics was observed in apo-variant G106W. Altogether, we here show that the area surrounding Gly106 constitutes the molecular switch involved in the conformational reorganization of EthR. These results also shed light on the mechanistic of ligand-induced allosterism controlling the DNA binding properties of TetR family repressors. Structural activation of the transcriptional repressor EthR from Mycobacterium tuberculosis by single amino acid change mimicking natural and synthetic ligands.,Carette X, Blondiaux N, Willery E, Hoos S, Lecat-Guillet N, Lens Z, Wohlkonig A, Wintjens R, Soror SH, Frenois F, Dirie B, Villeret V, England P, Lippens G, Deprez B, Locht C, Willand N, Baulard AR Nucleic Acids Res. 2011 Dec 9. PMID:22156370 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Tetracycline repressor protein 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA