5CG2
Crystal structure of E. coli FabI bound to the thiocarbamoylated benzodiazaborine inhibitor 35b.
Summary for 5CG2
| Entry DOI | 10.2210/pdb5cg2/pdb |
| Related | 5CFZ 5CG1 |
| Descriptor | Enoyl-[acyl-carrier-protein] reductase [NADH] FabI, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, 1-hydroxy-2,3,1-benzodiazaborinine-2(1H)-carbothioamide, ... (4 entities in total) |
| Functional Keywords | antibiotics, nad, enoyl-acp reductase, oxidoreducatase-oxidoreducatase inhibitor complex, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor |
| Biological source | Escherichia coli (strain K12) |
| Total number of polymer chains | 2 |
| Total formula weight | 67119.21 |
| Authors | Jordan, C.A.,Vey, J.L. (deposition date: 2015-07-09, release date: 2015-12-09, Last modification date: 2023-09-27) |
| Primary citation | Jordan, C.A.,Sandoval, B.A.,Serobyan, M.V.,Gilling, D.H.,Groziak, M.P.,Xu, H.H.,Vey, J.L. Crystallographic insights into the structure-activity relationships of diazaborine enoyl-ACP reductase inhibitors. Acta Crystallogr.,Sect.F, 71:1521-1530, 2015 Cited by PubMed Abstract: Enoyl-ACP reductase, the last enzyme of the fatty-acid biosynthetic pathway, is the molecular target for several successful antibiotics such as the tuberculosis therapeutic isoniazid. It is currently under investigation as a narrow-spectrum antibiotic target for the treatment of several types of bacterial infections. The diazaborine family is a group of boron heterocycle-based synthetic antibacterial inhibitors known to target enoyl-ACP reductase. Development of this class of molecules has thus far focused solely on the sulfonyl-containing versions. Here, the requirement for the sulfonyl group in the diazaborine scaffold was investigated by examining several recently characterized enoyl-ACP reductase inhibitors that lack the sulfonyl group and exhibit additional variability in substitutions, size and flexibility. Biochemical studies are reported showing the inhibition of Escherichia coli enoyl-ACP reductase by four diazaborines, and the crystal structures of two of the inhibitors bound to E. coli enoyl-ACP reductase solved to 2.07 and 2.11 Å resolution are reported. The results show that the sulfonyl group can be replaced with an amide or thioamide without disruption of the mode of inhibition of the molecule. PubMed: 26625295DOI: 10.1107/S2053230X15022098 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.11 Å) |
Structure validation
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