2F41

Crystal structure of FapR- a global regulator of fatty acid biosynthesis in B. subtilis

2F41 の概要

• エントリーDOI: 10.2210/pdb2f41/pdb
• 関連するPDBエントリー: 2F3X
• 分子名称: Transcription factor fapR (2 entities in total)
• 機能のキーワード: 'hot-dog' fold, gene regulation
• 由来する生物種: Bacillus subtilis
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 54060.98

構造登録者

Buschiazzo, A.,Guerin, M.E.,Alzari, P.M. (登録日: 2005-11-22, 公開日: 2006-10-31, 最終更新日: 2024-02-14)

主引用文献

Schujman, G.E.,Guerin, M.,Buschiazzo, A.,Schaeffer, F.,Llarrull, L.I.,Reh, G.,Vila, A.J.,Alzari, P.M.,de Mendoza, D.
Structural basis of lipid biosynthesis regulation in Gram-positive bacteria.
Embo J., 25:4074-4083, 2006

PubMed Abstract: Malonyl-CoA is an essential intermediate in fatty acid synthesis in all living cells. Here we demonstrate a new role for this molecule as a global regulator of lipid homeostasis in Gram-positive bacteria. Using in vitro transcription and binding studies, we demonstrate that malonyl-CoA is a direct and specific inducer of Bacillus subtilis FapR, a conserved transcriptional repressor that regulates the expression of several genes involved in bacterial fatty acid and phospholipid synthesis. The crystal structure of the effector-binding domain of FapR reveals a homodimeric protein with a thioesterase-like 'hot-dog' fold. Binding of malonyl-CoA promotes a disorder-to-order transition, which transforms an open ligand-binding groove into a long tunnel occupied by the effector molecule in the complex. This ligand-induced modification propagates to the helix-turn-helix motifs, impairing their productive association for DNA binding. Structure-based mutations that disrupt the FapR-malonyl-CoA interaction prevent DNA-binding regulation and result in a lethal phenotype in B. subtilis, suggesting this homeostatic signaling pathway as a promising target for novel chemotherapeutic agents against Gram-positive pathogens.

PubMed: 16932747
DOI: 10.1038/sj.emboj.7601284

実験手法

X-RAY DIFFRACTION (2.5 Å)