5CFZ

Crystal structure of E. coli FabI in apo form

5CFZ の概要

• エントリーDOI: 10.2210/pdb5cfz/pdb
• 関連するPDBエントリー: 5CG1 5CG2
• 分子名称: Enoyl-[acyl-carrier-protein] reductase [NADH] FabI (2 entities in total)
• 機能のキーワード: antibiotics, nad, enoyl-acp reductase, oxidoreducatase, oxidoreductase
• 由来する生物種: Escherichia coli (strain K12)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 65382.27

構造登録者

Jordan, C.A.,Vey, J.L. (登録日: 2015-07-08, 公開日: 2015-12-09, 最終更新日: 2023-09-27)

主引用文献

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

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: 26625295
DOI: 10.1107/S2053230X15022098

実験手法

X-RAY DIFFRACTION (1.97 Å)