5EY8

Structure of FadD32 from Mycobacterium smegmatis complexed to AMPC20

Summary for 5EY8

• Entry DOI: 10.2210/pdb5ey8/pdb
• Descriptor: Acyl-CoA synthase, [(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 (3 entities in total)
• Functional Keywords: ligase, fatty-acyl amp ligase
• Biological source: Mycobacterium smegmatis
• Total number of polymer chains: 8
• Total formula weight: 551658.21

Authors

Guillet, V.,Maveyraud, L.,Mourey, L. (deposition date: 2015-11-24, release date: 2015-12-16, Last modification date: 2024-05-08)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.5 Å)