Structure–Function Analysis of the Acyl Carrier Protein Synthase (AcpS) from Mycobacterium tuberculosis

Dym, Orly; Albeck, Shira; Peleg, Yoav; Schwarz, Alon; Shakked, Zippora; Burstein, Yigal; Zimhony, Oren

doi:10.1016/j.jmb.2009.08.065

Cited by 18 publications

(57 citation statements)

References 47 publications

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“…al. obtained an apo -AcpS structure that more closely resembled the “open” conformation, crystallized under similar pH conditions to Dym et al 150 The same helix movements observed by Dym et al 150 were observed in this new structure.…”

Section: Structuressupporting

confidence: 77%

“…X-ray crystal structures have been published of MtAcpS, 150 showing that the protein undergoes conformational changes at pHs >6.5, with resultant decreases in AcpS activity. 151 The intracellular pH of mycobacteria is between 6.1–7.2, even when exposed to acid or base, 152 and although purely speculative, it might be that siderophore or other natural product production is regulated by the activity of the PPTase.…”

Section: Importance In Primary and Secondary Metabolismmentioning

confidence: 99%

“…A structure containing 3′,5′-ADP was initially solved by Dym et al 150 When compared to other AcpS structures, several regions were absent in the electron density including residues 22–30, 41–44 and 75–78. Additionally, α-helix 3 extends further than other AcpSs.…”

Section: Structuresmentioning

confidence: 99%

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The phosphopantetheinyl transferases: catalysis of a post-translational modification crucial for life

et al. 2014

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Although holo-acyl carrier protein synthase, AcpS, a phosphopantetheinyl transferase (PPTase), was characterized in the 1960s, it was not until the publication of the landmark paper by Lambalot et al. in 1996 that PPTases garnered wide-spread attention being classified as a distinct enzyme superfamily. In the past two decades an increasing number of papers has been published on PPTases ranging from identification, characterization, structure determination, mutagenesis, inhibition, and engineering in synthetic biology. In this review, we comprehensively discuss all current knowledge on this class of enzymes that post-translationally install a 4′-phosphopantetheine arm on various carrier proteins.

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Section: Structuressupporting

confidence: 77%

Section: Importance In Primary and Secondary Metabolismmentioning

confidence: 99%

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The phosphopantetheinyl transferases: catalysis of a post-translational modification crucial for life

et al. 2014

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“…It not only lacks many of the structural domains and expansion segments but also the C-terminal PPT domain, which in this case is encoded by a separate gene located immediately downstream of the fas gene and obviously can act in trans (Fig. 8) (Chopra et al 2002;Dym et al 2009 ;Schweizer & Hofmann, 2004). (a) The b-chain is formed by consecutive globular domains, whereas the a-chain adopts a highly intertwined structure with numerous insertions into the KS domain and a complex extension of the KR, which together form the rigid scaffold of the central wheel.…”

Section: Overall Architecturementioning

confidence: 99%

Structure and function of eukaryotic fatty acid synthases

Maier

Leibundgut

Boehringer

et al. 2010

Quart. Rev. Biophys.

123

127

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Abstract. In all organisms, fatty acid synthesis is achieved in variations of a common cyclic reaction pathway by stepwise, iterative elongation of precursors with two-carbon extender units. In bacteria, all individual reaction steps are carried out by monofunctional dissociated enzymes, whereas in eukaryotes the fatty acid synthases (FASs) have evolved into large multifunctional enzymes that integrate the whole process of fatty acid synthesis. During the last few years, important advances in understanding the structural and functional organization of eukaryotic FASs have been made through a combination of biochemical, electron microscopic and X-ray crystallographic approaches. They have revealed the strikingly different architectures of the two distinct types of eukaryotic FASs, the fungal and the animal enzyme system. Fungal FAS is a 2Á6 MDa a 6 b 6 heterododecamer with a barrel shape enclosing two large chambers, each containing three sets of active sites separated by a central wheel-like structure. It represents a highly specialized micro-compartment strictly optimized for the production of saturated fatty acids. In contrast, the animal FAS is a 540 kDa X-shaped homodimer with two lateral reaction clefts characterized by a modular domain architecture and large extent of conformational flexibility that appears to contribute to catalytic efficiency.

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“…Three families of PPT enzymes have been characterized to date, primarily from microbial sources. Family I PPT is typified by the E. coli ACP synthase (AcpS) (Elovson and Vagelos, 1968;Lambalot and Walsh, 1995), which functions as a homotrimeric complex (Chirgadze et al, 2000;Parris et al, 2000;Dym et al, 2009;Gokulan et al, 2011) to posttranslationally modify apo-ACP. Family II PPT is typified by the Bacillus subtilis Sfp enzyme (Nakano et al, 1992), which is a monomer consisting of two domains, each of which structurally mimic an AcpS monomer, with a single active site situated at the interface of the two domains (Reuter et al, 1999;Bunkoczi et al, 2007;Tufar et al, 2014;Vickery et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

A phosphopantetheinyl transferase that is essential for mitochondrial fatty acid biosynthesis

et al. 2015

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SUMMARYIn this study we report the molecular genetic characterization of the Arabidopsis mitochondrial phosphopantetheinyl transferase (mtPPT), which catalyzes the phosphopantetheinylation and thus activation of mitochondrial acyl carrier protein (mtACP) of mitochondrial fatty acid synthase (mtFAS). This catalytic capability of the purified mtPPT protein (encoded by AT3G11470) was directly demonstrated in an in vitro assay that phosphopantetheinylated mature Arabidopsis apo-mtACP isoforms. The mitochondrial localization of the AT3G11470-encoded proteins was validated by the ability of their N-terminal 80-residue leader sequence to guide a chimeric GFP protein to this organelle. A T-DNA-tagged null mutant mtppt-1 allele shows an embryo-lethal phenotype, illustrating a crucial role of mtPPT for embryogenesis. Arabidopsis RNAi transgenic lines with reduced mtPPT expression display typical phenotypes associated with a deficiency in the mtFAS system, namely miniaturized plant morphology, slow growth, reduced lipoylation of mitochondrial proteins, and the hyperaccumulation of photorespiratory intermediates, glycine and glycolate. These morphological and metabolic alterations are reversed when these plants are grown in a non-photorespiratory condition (i.e. 1% CO 2 atmosphere), demonstrating that they are a consequence of a deficiency in photorespiration due to the reduced lipoylation of the photorespiratory glycine decarboxylase.

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Structure–Function Analysis of the Acyl Carrier Protein Synthase (AcpS) from Mycobacterium tuberculosis

Cited by 18 publications

References 47 publications

The phosphopantetheinyl transferases: catalysis of a post-translational modification crucial for life

The phosphopantetheinyl transferases: catalysis of a post-translational modification crucial for life

Structure and function of eukaryotic fatty acid synthases

A phosphopantetheinyl transferase that is essential for mitochondrial fatty acid biosynthesis

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