1MFP

E. coli Enoyl Reductase in complex with NAD and SB611113

1MFP の概要

• エントリーDOI: 10.2210/pdb1mfp/pdb
• 関連するPDBエントリー: 1C14 1I2Z 1I30
• 分子名称: enoyl-[acyl-carrier-protein] reductase [Nadh], NICOTINAMIDE-ADENINE-DINUCLEOTIDE, (E)-N-METHYL-N-(1-METHYL-1H-INDOL-3-YLMETHYL)-3-(7-OXO-5,6,7,8-TETRAHYDRO-[1,8]NAPHTHYRIDIN-3-YL)-ACRYLAMIDE, ... (5 entities in total)
• 機能のキーワード: fabi, enoyl reductase, enoyl-acp reductase, oxidoreductase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 57957.64

構造登録者

Seefeld, M.A.,Miller, W.H.,Newlander, K.A.,Burgess, W.J.,DeWolf Jr., W.E.,Elkins, P.A.,Head, M.S.,Jakas, D.R.,Janson, C.A.,Keller, P.M.,Manley, P.J.,Moore, T.D.,Payne, D.J.,Pearson, S.,Polizzi, B.J.,Qiu, X.,Rittenhouse, S.F.,Uzinskas, I.N.,Wallis, N.G.,Huffman, W.F. (登録日: 2002-08-13, 公開日: 2003-05-06, 最終更新日: 2024-02-14)

主引用文献

Seefeld, M.A.,Miller, W.H.,Newlander, K.A.,Burgess, W.J.,DeWolf Jr., W.E.,Elkins, P.A.,Head, M.S.,Jakas, D.R.,Janson, C.A.,Keller, P.M.,Manley, P.J.,Moore, T.D.,Payne, D.J.,Pearson, S.,Polizzi, B.J.,Qiu, X.,Rittenhouse, S.F.,Uzinskas, I.N.,Wallis, N.G.,Huffman, W.F.
Indole Naphthyridinones as Inhibitors of Bacterial Enoyl-ACP Reductases FabI and FabK
J.MED.CHEM., 46:1627-1635, 2003

PubMed Abstract: Bacterial enoyl-ACP reductase (FabI) is responsible for catalyzing the final step of bacterial fatty acid biosynthesis and is an attractive target for the development of novel antibacterial agents. Previously we reported the development of FabI inhibitor 4 with narrow spectrum antimicrobial activity and in vivo efficacy against Staphylococcus aureus via intraperitoneal (ip) administration. Through iterative medicinal chemistry aided by X-ray crystal structure analysis, a new series of inhibitors has been developed with greatly increased potency against FabI-containing organisms. Several of these new inhibitors have potent antibacterial activity against multidrug resistant strains of S. aureus, and compound 30 demonstrates exceptional oral (po) in vivo efficacy in a S. aureus infection model in rats. While optimizing FabI inhibitory activity, compounds 29 and 30 were identified as having low micromolar FabK inhibitory activity, thereby increasing the antimicrobial spectrum of these compounds to include the FabK-containing pathogens Streptococcus pneumoniae and Enterococcus faecalis. The results described herein support the hypothesis that bacterial enoyl-ACP reductases are valid targets for antibacterial agents.

PubMed: 12699381
DOI: 10.1021/jm0204035

実験手法

X-RAY DIFFRACTION (2.33 Å)