8OTL
structure of InhA from Mycobacterium tuberculosis in complex with 5-(((4-(2-hydroxyphenoxy)benzyl)(octyl)amino)methyl)-2-phenoxyphenol
Summary for 8OTL
| Entry DOI | 10.2210/pdb8otl/pdb |
| Descriptor | Enoyl-[acyl-carrier-protein] reductase [NADH], NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ACETATE ION, ... (6 entities in total) |
| Functional Keywords | enoyl-acp-reductase type ii fatty acid synthase mycolic acids tuberculosis therapeutic target, oxidoreductase |
| Biological source | Mycobacterium tuberculosis |
| Total number of polymer chains | 6 |
| Total formula weight | 177770.79 |
| Authors | Tamhaev, R.,Maveyraud, L.,Chebaiki, M.,Lherbet, C.,Mourey, L. (deposition date: 2023-04-21, release date: 2024-01-24) |
| Primary citation | Tamhaev, R.,Grosjean, E.,Ahamed, H.,Chebaiki, M.,Rodriguez, F.,Recchia, D.,Degiacomi, G.,Pasca, M.R.,Maveyraud, L.,Mourey, L.,Lherbet, C. Exploring the plasticity of the InhA substrate-binding site using new diaryl ether inhibitors. Bioorg.Chem., 143:107032-107032, 2023 Cited by PubMed Abstract: 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 of 0.70 µM. 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. PubMed: 38128204DOI: 10.1016/j.bioorg.2023.107032 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.108 Å) |
Structure validation
Download full validation report
