Abstract
While a deep understanding of the fungal and mammalian multi-enzyme type I fatty-acid synthases (FAS I) has been achieved in recent years, the bacterial FAS I family, which is narrowly distributed within the Actinomycetales genera Mycobacterium, Corynebacterium and Nocardia, is still poorly understood. This is of particular relevance for two reasons: (i) although homologous to fungal FAS I, cryo-electron microscopic studies have shown that bacterial FAS I has unique structural and functional properties, and (ii) M. tuberculosis FAS I is a drug target for the therapeutic treatment of tuberculosis (TB) and therefore is of extraordinary importance as a drug target. Crystals of FAS I from C. efficiens, a homologue of M. tuberculosis FAS I, were produced and diffracted X-rays to about 4.5 Å resolution.
Highlights
Fatty acids are important as principal components of cellular membranes, as post-translational modifiers of proteins, as a storage form of energy and as signalling molecules
While a deep understanding of the fungal and mammalian multi-enzyme type I fatty-acid synthases (FAS I) has been achieved in recent years, the bacterial FAS I family, which is narrowly distributed within the Actinomycetales genera Mycobacterium, Corynebacterium and Nocardia, is still poorly understood
This is of particular relevance for two reasons: (i) homologous to fungal FAS I, cryo-electron microscopic studies have shown that bacterial FAS I has unique structural and functional properties, and (ii) M. tuberculosis FAS I is a drug target for the therapeutic treatment of tuberculosis (TB) and is of extraordinary importance as a drug target
Summary
Fatty acids are important as principal components of cellular membranes, as post-translational modifiers of proteins, as a storage form of energy and as signalling molecules. Despite the conservation of the chemistry of synthesis, the structures of fatty-acid synthases (FAS) differ significantly in eukaryotes and bacteria. The other ‘conventional’ FAS system that is present in most bacteria and mitochondria is referred to as type II, in which separate monofunctional proteins perform the specific steps required for fatty-acid synthesis (Schweizer & Hofmann, 2004; Gago et al, 2011). FAS type I multi-enzyme complexes have been extensively analyzed in recent years by X-ray crystallographic and cryoelectron microscopic (cryo-EM) studies (Maier et al, 2010; Grininger, 2014). Cryo-EM studies of the conformational dynamics contributed to the structural knowledge of FAS I systems (Brignole et al, 2009; Gipson et al, 2010; Ciccarelli et al, 2013), by showing that bacterial and mammalian FAS I are conformationally dynamic, which critically determines their molecular mode (Grininger, 2014). We present the expression, purification, thermal stability data, crystallization and preliminary X-ray analysis of FAS I from C. efficiens
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