6SQ5
Crystal structure of M. tuberculosis InhA in complex with NAD+ and 3-[3-(trifluoromethyl)phenyl]prop-2-enoic acid
Summary for 6SQ5
| Entry DOI | 10.2210/pdb6sq5/pdb |
| Descriptor | Enoyl-[acyl-carrier-protein] reductase [NADH], NICOTINAMIDE-ADENINE-DINUCLEOTIDE, (~{E})-3-[3-(trifluoromethyl)phenyl]prop-2-enoic acid, ... (4 entities in total) |
| Functional Keywords | inha, nadh-dependent enoyl-[acyl-carrier-protein] reductase, oxidoreductase |
| Biological source | Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
| Total number of polymer chains | 1 |
| Total formula weight | 29521.44 |
| Authors | Mendes, V.,Sabbah, M.,Coyne, A.G.,Abell, C.,Blundell, T.L. (deposition date: 2019-09-03, release date: 2020-04-22, Last modification date: 2024-01-24) |
| Primary citation | Sabbah, M.,Mendes, V.,Vistal, R.G.,Dias, D.M.G.,Zahorszka, M.,Mikusova, K.,Kordulakova, J.,Coyne, A.G.,Blundell, T.L.,Abell, C. Fragment-Based Design ofMycobacterium tuberculosisInhA Inhibitors. J.Med.Chem., 63:4749-4761, 2020 Cited by PubMed Abstract: Tuberculosis (TB) remains a leading cause of mortality among infectious diseases worldwide. InhA has been the focus of numerous drug discovery efforts as this is the target of the first line pro-drug isoniazid. However, with resistance to this drug becoming more common, the aim has been to find new clinical candidates that directly inhibit this enzyme and that do not require activation by the catalase peroxidase KatG, thus circumventing the majority of the resistance mechanisms. In this work, the screening and validation of a fragment library are described, and the development of the fragment hits using a fragment growing strategy was employed, which led to the development of InhA inhibitors with affinities of up to 250 nM. PubMed: 32240584DOI: 10.1021/acs.jmedchem.0c00007 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.84 Å) |
Structure validation
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