5EY9

Structure of FadD32 from Mycobacterium marinum complexed to AMPC12

5EY9 の概要

• エントリーDOI: 10.2210/pdb5ey9/pdb
• 分子名称: Long-chain-fatty-acid--AMP ligase FadD32, [(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl icosyl hydrogen phosphate, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: ligase, fatty-acyl amp ligase
• 由来する生物種: Mycobacterium marinum
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 139843.10

構造登録者

Guillet, V.,Maveyraud, L.,Mourey, L. (登録日: 2015-11-24, 公開日: 2015-12-16, 最終更新日: 2024-01-10)

主引用文献

Guillet, V.,Galandrin, S.,Maveyraud, L.,Ladeveze, S.,Mariaule, V.,Bon, C.,Eynard, N.,Daffe, M.,Marrakchi, H.,Mourey, L.
Insight into Structure-Function Relationships and Inhibition of the Fatty Acyl-AMP Ligase (FadD32) Orthologs from Mycobacteria.
J.Biol.Chem., 291:7973-7989, 2016

PubMed Abstract: Mycolic acids are essential components of the mycobacterial cell envelope, and their biosynthetic pathway is one of the targets of first-line antituberculous drugs. This pathway contains a number of potential targets, including some that have been identified only recently and have yet to be explored. One such target, FadD32, is required for activation of the long meromycolic chain and is essential for mycobacterial growth. We report here an in-depth biochemical, biophysical, and structural characterization of four FadD32 orthologs, including the very homologous enzymes fromMycobacterium tuberculosisandMycobacterium marinum Determination of the structures of two complexes with alkyl adenylate inhibitors has provided direct information, with unprecedented detail, about the active site of the enzyme and the associated hydrophobic tunnel, shedding new light on structure-function relationships and inhibition mechanisms by alkyl adenylates and diarylated coumarins. This work should pave the way for the rational design of inhibitors of FadD32, a highly promising drug target.

PubMed: 26900152
DOI: 10.1074/jbc.M115.712612

実験手法

X-RAY DIFFRACTION (2.5 Å)