5ey9 | pdb_00005ey9
Structure of FadD32 from Mycobacterium marinum complexed to AMPC12
Structural highlights
Function[FAA32_MYCMM] Catalyzes the activation of long-chain fatty acids as acyl-adenylates (acyl-AMP), which are then transferred to the multifunctional polyketide synthase (PKS) for further chain extension. Publication Abstract from PubMedMycolic 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. Insight into Structure-Function Relationships and Inhibition of the Fatty Acyl-AMP Ligase (FadD32) Orthologs from Mycobacteria.,Guillet V, Galandrin S, Maveyraud L, Ladeveze S, Mariaule V, Bon C, Eynard N, Daffe M, Marrakchi H, Mourey L J Biol Chem. 2016 Apr 8;291(15):7973-89. doi: 10.1074/jbc.M115.712612. Epub 2016 , Feb 21. PMID:26900152[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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