title: Negative regulation by Ser/Thr phosphorylation of HadAB and HadBC dehydratases from Mycobacterium tuberculosis type II fatty acid synthase system.
abstract: The type II fatty acid synthase system of mycobacteria is involved in the biosynthesis of major and essential lipids, mycolic acids, key-factors of Mycobacterium tuberculosis pathogenicity. One reason of the remarkable survival ability of M. tuberculosis in infected hosts is partly related to the presence of cell wall-associated mycolic acids. Despite their importance, the mechanisms that modulate synthesis of these lipids in response to environmental changes are unknown. We demonstrate here that HadAB and HadBC dehydratases of this system are phosphorylated by Ser/Thr protein kinases, which negatively affects their enzymatic activity. The phosphorylation of HadAB/BC is growth phase-dependent, suggesting that it represents a mechanism by which mycobacteria might tightly control mycolic acid biosynthesis under non-replicating condition.
authors.affiliation: CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), Département Mécanismes Moléculaires des Infections Mycobactériennes, 205 Route de Narbonne, F-31077 Toulouse, France.
authors.forename: Nawel
authors.initials: N
authors.lastname: Slama
authors.forename: Jade
authors.initials: J
authors.lastname: Leiba
authors.forename: Nathalie
authors.initials: N
authors.lastname: Eynard
authors.forename: Mamadou
authors.initials: M
authors.lastname: Daffé
authors.forename: Laurent
authors.initials: L
authors.lastname: Kremer
authors.forename: Annaïk
authors.initials: A
authors.lastname: Quémard
authors.forename: Virginie
authors.initials: V
authors.lastname: Molle
mesh_terms: D000595:Amino Acid Sequence; D015536:Down-Regulation; D054889:Fatty Acid Synthase, Type II / Q000235:genetics / Q000378:metabolism*; D006836:Hydro-Lyases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism; D013912:Threonine / Q000378:metabolism
chemical_list: D013912:Threonine; D012694:Serine; D006836:Hydro-Lyases; C047118:3-hydroxyacyl-(acyl-carrier-protein) dehydratase; D054889:Fatty Acid Synthase, Type II