3o8h

EthR from Mycobacterium tuberculosis in complex with compound BDM14950

spinqualitylabelsall models 3o8h, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3o8h is a 1 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: O8H Related: 1u9n, 3o8g Gene: ethR, MT3970, Rv3855 (Mycobacterium tuberculosis) Resources: FirstGlance, OCA, RCSB, PDBsum Function [P96222_MYCTU] Involved in the repression of the monooxygenase EthA which is responsible of the formation of the active metabolite of ethionamide (ETH). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed In situ click chemistry has been successfully applied to probe the ligand binding domain of EthR, a mycobacterial transcriptional regulator known to control the sensitivity of Mycobacterium tuberculosis to several antibiotics. Specific protein-templated ligands were generated in situ from one azide and six clusters of 10 acetylenic fragments. Comparative X-ray structures of EthR complexed with either clicked ligand BDM14950 or its azide precursor showed ligand-dependent conformational impacts on the protein architecture. This approach revealed two mobile phenylalanine residues that control the access to a previously hidden hydrophobic pocket that can be further exploited for the development of structurally diverse EthR inhibitors. This report shows that protein-directed in situ chemistry allows medicinal chemists to explore the conformational space of a ligand-binding pocket and is thus a valuable tool to guide drug design in the complex path of hit-to-lead processes. Exploring Drug Target Flexibility Using in Situ Click Chemistry: Application to a Mycobacterial Transcriptional Regulator.,Willand N, Desroses M, Toto P, Dirie B, Lens Z, Villeret V, Rucktooa P, Locht C, Baulard A, Deprez B ACS Chem Biol. 2010 Aug 26. PMID:20704273 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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