4tro | pdb_00004tro

Structure of the enoyl-ACP reductase of Mycobacterium tuberculosis InhA, inhibited with the active metabolite of isoniazid

spinqualitylabelsall models 4tro, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4tro 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. Method: X-ray diffraction, Resolution 1.4Å Ligands: DMS, EPE, NA, NAD, ZID Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function INHA_MYCTU Publication Abstract from PubMed 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 1.80A resolution as well as the crystal structure of InhA in complex with the synthetic metabolite of the antitubercular drug isoniazid refined to 1.40A. 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. 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.,Chollet A, Mourey L, Lherbet C, Delbot A, Julien S, Baltas M, Bernadou J, Pratviel G, Maveyraud L, Bernardes-Genisson V J Struct Biol. 2015 Apr 17. pii: S1047-8477(15)00080-5. doi:, 10.1016/j.jsb.2015.04.008. PMID:25891098 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Enoyl-Acyl-Carrier Protein Reductase 3D structures

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