7e48 | pdb_00007e48

Crystal structure of InhA in complex with 3-nitropropanoic acid inhibitor

spinqualitylabelsall models 7e48, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7e48 is a 4 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5Å Ligands: 3NP, GOL, NAD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function INHA_MYCTU Publication Abstract from PubMed 3-Nitropropanoic acid (3NP), a bioactive fungal natural product, was previously demonstrated to inhibit growth of Mycobacterium tuberculosis. Here we demonstrate that 3NP inhibits the 2-trans-enoyl-acyl carrier protein reductase (InhA) from Mycobacterium tuberculosis with an IC50 value of 71 muM, and present the crystal structure of the ternary InhA-NAD(+) -3NP complex. The complex contains the InhA substrate-binding loop in an ordered, open conformation with Tyr158, a catalytically important residue whose orientation defines different InhA substrate/inhibitor complex conformations, in the "out" position. 3NP occupies a hydrophobic binding site adjacent to the NAD(+) cofactor and close to that utilized by the diphenyl ether triclosan, but binds predominantly via electrostatic and water-mediated hydrogen-bonding interactions with the protein backbone and NAD(+) cofactor. The identified mode of 3NP binding provides opportunities to improve inhibitory activity toward InhA. Inhibition of Mycobacterium tuberculosis InhA by 3-nitropropanoic acid.,Songsiriritthigul C, Hanwarinroj C, Pakamwong B, Srimanote P, Suttipanta N, Sureram S, Suttisintong K, Kamsri P, Punkvang A, Spencer J, Kittakoop P, Pungpo P Proteins. 2021 Oct 22. doi: 10.1002/prot.26268. PMID:34677871 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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