4TRN
STRUCTURE OF INHA FROM MYCOBACTERIUM TUBERCULOSIS COMPLEXED TO NADH
Summary for 4TRN
| Entry DOI | 10.2210/pdb4trn/pdb |
| Related | 4TRM 4TRO |
| Descriptor | INHA, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (5 entities in total) |
| Functional Keywords | enoyl acp reductase, oxidoreductase |
| Biological source | Mycobacterium tuberculosis |
| Total number of polymer chains | 1 |
| Total formula weight | 29492.65 |
| Authors | Chollet, A.,Julien, S.,Mourey, L.,Maveyraud, L. (deposition date: 2014-06-17, release date: 2015-04-29, Last modification date: 2023-12-20) |
| Primary citation | Chollet, A.,Mourey, L.,Lherbet, C.,Delbot, A.,Julien, S.,Baltas, M.,Bernadou, J.,Pratviel, G.,Maveyraud, L.,Bernardes-Genisson, V. Crystal structure of the enoyl-ACP reductase of Mycobacterium tuberculosis (InhA) in the apo-form and in complex with the active metabolite of isoniazid pre-formed by a biomimetic approach. J.Struct.Biol., 190:328-337, 2015 Cited by PubMed Abstract: InhA is an enoyl-ACP reductase of Mycobacterium tuberculosis implicated in the biosynthesis of mycolic acids, essential constituents of the mycobacterial cell wall. To date, this enzyme is considered as a promising target for the discovery of novel antitubercular drugs. In this work, we describe the first crystal structure of the apo form of the wild-type InhA at 1.80Å resolution as well as the crystal structure of InhA in complex with the synthetic metabolite of the antitubercular drug isoniazid refined to 1.40Å. This metabolite, synthesized in the absence of InhA, is able to displace and replace the cofactor NADH in the enzyme active site. This work provides a unique opportunity to enlighten the structural adaptation of apo-InhA to the binding of the NADH cofactor or of the isoniazid adduct. In addition, a differential scanning fluorimetry study of InhA, in the apo-form as well as in the presence of NAD(+), NADH and INH-NADH was performed showing that binding of the INH-NADH adduct had a strong stabilizing effect. PubMed: 25891098DOI: 10.1016/j.jsb.2015.04.008 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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