8otl

structure of InhA from Mycobacterium tuberculosis in complex with 5-(((4-(2-hydroxyphenoxy)benzyl)(octyl)amino)methyl)-2-phenoxyphenol

spinqualitylabelsall models 8otl, resolution 2.11Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8otl is a 6 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.108Å Ligands: ACT, EDO, NAD, VZE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function INHA_MYCTU Publication Abstract from PubMed Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a worldwide scourge with more than 10 million people affected yearly. Among the proteins essential for the survival of Mtb, InhA has been and is still clinically validated as a therapeutic target. A new family of direct diaryl ether inhibitors, not requiring prior activation by the catalase peroxidase enzyme KatG, has been designed with the ambition of fully occupying the InhA substrate-binding site. Thus, eleven compounds, featuring three pharmacophores within the same molecule, were synthesized. One of them, 5-(((4-(2-hydroxyphenoxy)benzyl)(octyl)amino)methyl)-2-phenoxyphenol (compound 21), showed good inhibitory activity against InhA with IC(50) of 0.70 microM. The crystal structure of compound 21 in complex with InhA/NAD(+) showed how the molecule fills the substrate-binding site as well as the minor portal of InhA. This study represents a further step towards the design of new inhibitors of InhA. Exploring the plasticity of the InhA substrate-binding site using new diaryl ether inhibitors.,Tamhaev R, Grosjean E, Ahamed H, Chebaiki M, Rodriguez F, Recchia D, Degiacomi G, Pasca MR, Maveyraud L, Mourey L, Lherbet C Bioorg Chem. 2024 Feb;143:107032. doi: 10.1016/j.bioorg.2023.107032. Epub 2023 , Dec 12. PMID:38128204 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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