Acetyl-CoA Synthetase from the Amitochondriate EukaryoteGiardia lamblia Belongs to the Newly Recognized Superfamily of Acyl-CoA Synthetases (Nucleoside Diphosphate-forming)

Sánchez, Lidya B.; Galperin, Michael Y.; Müller, Miklós

doi:10.1074/jbc.275.8.5794

Cited by 104 publications

(124 citation statements)

References 40 publications

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“…ACL catalyzes the reverse of the CS-catalyzed reaction, and is a member of a thiokinase superfamily, along with SCS, acetyl-CoA synthetase, and malate thiokinase (Sanchez et al, 2000). This functional similarity is translated to conservation in the primary structure of these proteins.…”

Section: Discussionmentioning

confidence: 99%

“…These motifs partially encompass the putative ATP-binding site (red bar), and a potential CoA-binding site (blue bar). Other conserved residues across ACL and SCS are Lys 3, Lys 58, Glu 116, and Asp 213 of Arabidopsis ACLA, conserved in the ATP-grasp domains (Fraser et al, 1999;Sanchez et al, 2000), and Gln 24, Pro 46, Ala 86, Arg 175, Asp 212, and Glu 232 of ACLB shown to be critical in the active site in SCS (Wolodko et al, 1994;Fraser et al, 1999; purple arrows). Ala 97 in Arabidopsis ACLB is the plant nonconservative substitution for otherwise conserved Glu.…”

Section: Discussionmentioning

confidence: 99%

“…Based upon sequence conservation between ACL and SCS subunits, as well as sequence conservation between ACL and CS, ACL may have arisen from the evolutionary fusion and subsequent adaptation of domains from SCS and CS (Sanchez et al, 2000). The ancestral ACLA protein appears to have arisen via the divergence of the SCS ␤-subunit (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Molecular Characterization of a Heteromeric ATP-Citrate Lyase That Generates Cytosolic Acetyl-Coenzyme A in Arabidopsis,

Fatland¹,

Ke²,

Anderson³

et al. 2002

Plant Physiology

189

191

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Acetyl-coenzyme A (CoA) is used in the cytosol of plant cells for the synthesis of a diverse set of phytochemicals including waxes, isoprenoids, stilbenes, and flavonoids. The source of cytosolic acetyl-CoA is unclear. We identified two Arabidopsis cDNAs that encode proteins similar to the amino and carboxy portions of human ATP-citrate lyase (ACL). Coexpression of these cDNAs in yeast (Saccharomyces cerevisiae) confers ACL activity, indicating that both the Arabidopsis genes are required for ACL activity. Arabidopsis ACL is a heteromeric enzyme composed of two distinct subunits, ACLA (45 kD) and ACLB (65 kD). The holoprotein has a molecular mass of 500 kD, which corresponds to a heterooctomer with an A 4 B 4 configuration. ACL activity and the ACLA and ACLB polypeptides are located in the cytosol, consistent with the lack of targeting peptides in the ACLA and ACLB sequences. In the Arabidopsis genome, three genes encode for the ACLA subunit (ACLA-1, At1g10670; ACLA-2, At1g60810; and ACLA-3, At1g09430), and two genes encode the ACLB subunit (ACLB-1, At3g06650 and ACLB-2, At5g49460). The ACLA and ACLB mRNAs accumulate in coordinated spatial and temporal patterns during plant development. This complex accumulation pattern is consistent with the predicted physiological needs for cytosolic acetyl-CoA, and is closely coordinated with the accumulation pattern of cytosolic acetyl-CoA carboxylase, an enzyme using cytosolic acetyl-CoA as a substrate. Taken together, these results indicate that ACL, encoded by the ACLA and ACLB genes of Arabidopsis, generates cytosolic acetyl-CoA. The heteromeric organization of this enzyme is common to green plants (including Chlorophyceae, Marchantimorpha, Bryopsida, Pinaceae, monocotyledons, and eudicots), species of fungi, Glaucophytes, Chlamydomonas, and prokaryotes. In contrast, all known animal ACL enzymes have a homomeric structure, indicating that a evolutionary fusion of the ACLA and ACLB genes probably occurred early in the evolutionary history of this kingdom.Acetyl-coenzyme A (CoA) is an intermediate metabolite that is juxtaposed between catabolic and anabolic processes. As the entry point for the tricarboxylic acid (TCA) cycle, acetyl-CoA can be considered the gateway in the oxidation of carbon derived from the catabolism of fatty acids, certain amino acids (e.g. Leu, Ile, Lys, and Trp), and carbohydrates. Furthermore, acetyl-CoA is the intermediate precursor for the biosynthesis of a wide variety of phytochemicals. Because membranes are impermeable to CoA derivatives, it can be inferred that acetyl-CoA is generated in at least four distinct metabolic pools representing the four subcellular compartments where acetyl-CoA metabolism occurs: plastids, mitochondria, peroxisomes, and the cytosol (Fig. 1). Therefore, plants should have distinct acetyl-CoA-generating systems in mitochondria (for the TCA cycle), in plastids (for de novo fatty acid biosynthesis), in peroxisomes (the product of ␤-oxidation of fatty acids), and in the cytosol (for the biosynthesis of isoprenoids, flavo...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular Characterization of a Heteromeric ATP-Citrate Lyase That Generates Cytosolic Acetyl-Coenzyme A in Arabidopsis,

Fatland¹,

Ke²,

Anderson³

et al. 2002

Plant Physiology

189

191

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“…But it was also well-known early on (Zillig 1991) that equally numerous, possibly even more (Rivera et al 1998), traits link eukaryotes and eubacteria. In some anaerobic protists, traces of the archaebacterial host lineage have been retained in energy metabolism as well (see Hannaert et al 2000;Sanchez et al 2000;Suguri et al 2001), clearly indicating mosaicism in eukaryotic biochemistry. Zillig (1991) argued that eukaryotes acquired their eubacterial traits, including lipid biosynthesis and some of their glycolytic genes, from a eubacterial symbiont; but because he thought that Giardia was primitively amitochondriate, he invoked a eubacterial donor that was distinct from the mitochondrion.…”

Section: Getting Accustomed To the Possibility Of A Prokaryotic And Amentioning

confidence: 99%

On the origins of cells: a hypothesis for the evolutionary transitions from abiotic geochemistry to chemoautotrophic prokaryotes, and from prokaryotes to nucleated cells

Martin

Russell

2003

Phil. Trans. R. Soc. Lond. B

704

613

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All life is organized as cells. Physical compartmentation from the environment and self-organization of self-contained redox reactions are the most conserved attributes of living things, hence inorganic matter with such attributes would be life's most likely forebear. We propose that life evolved in structured iron monosulphide precipitates in a seepage site hydrothermal mound at a redox, pH and temperature gradient between sulphide-rich hydrothermal fluid and iron(II)-containing waters of the Hadean ocean floor. The naturally arising, three-dimensional compartmentation observed within fossilized seepage-site metal sulphide precipitates indicates that these inorganic compartments were the precursors of cell walls and membranes found in free-living prokaryotes. The known capability of FeS and NiS to catalyse the synthesis of the acetyl-methylsulphide from carbon monoxide and methylsulphide, constituents of hydrothermal fluid, indicates that pre-biotic syntheses occurred at the inner surfaces of these metal-sulphide-walled compartments, which furthermore restrained reacted products from diffusion into the ocean, providing sufficient concentrations of reactants to forge the transition from geochemistry to biochemistry. The chemistry of what is known as the RNA-world could have taken place within these naturally forming, catalyticwalled compartments to give rise to replicating systems. Sufficient concentrations of precursors to support replication would have been synthesized in situ geochemically and biogeochemically, with FeS (and NiS) centres playing the central catalytic role. The universal ancestor we infer was not a free-living cell, but rather was confined to the naturally chemiosmotic, FeS compartments within which the synthesis of its constituents occurred. The first free-living cells are suggested to have been eubacterial and archaebacterial chemoautotrophs that emerged more than 3.8 Gyr ago from their inorganic confines. We propose that the emergence of these prokaryotic lineages from inorganic confines occurred independently, facilitated by the independent origins of membrane-lipid biosynthesis: isoprenoid ether membranes in the archaebacterial and fatty acid ester membranes in the eubacterial lineage. The eukaryotes, all of which are ancestrally heterotrophs and possess eubacterial lipids, are suggested to have arisen ca. 2 Gyr ago through symbiosis involving an autotrophic archaebacterial host and a heterotrophic eubacterial symbiont, the common ancestor of mitochondria and hydrogenosomes. The attributes shared by all prokaryotes are viewed as inheritances from their confined universal ancestor. The attributes that distinguish eubacteria and archaebacteria, yet are uniform within the groups, are viewed as relics of their phase of differentiation after divergence from the non-free-living universal ancestor and before the origin of the free-living chemoautotrophic lifestyle. The attributes shared by eukaryotes with eubacteria and archaebacteria, respectively, are viewed as inheritances via symbiosis. The ...

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“…In bacteria, with the exception of Chloroflexus (9), the conversion of inorganic phosphate and the thioester acetyl (Ac)-CoA to acetate and ATP is catalyzed by two enzymes, phosphate Ac-transferase and acetate kinase (10). Following the identification of ACD genes (5, 11) a novel protein superfamily of NDP-forming ACDs was proposed by a bioinformatics analysis (8). In addition to ACDs, this superfamily contains the wellcharacterized succinyl-CoA synthetases (SCSs) and ATP-citrate lyases (ACLYs) (8).…”

mentioning

confidence: 99%

Structure of NDP-forming Acetyl-CoA synthetase ACD1 reveals a large rearrangement for phosphoryl transfer

Weisse

Faust

Schmidt

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The NDP-forming acyl-CoA synthetases (ACDs) catalyze the conversion of various CoA thioesters to the corresponding acids, conserving their chemical energy in form of ATP. The ACDs are the major energy-conserving enzymes in sugar and peptide fermentation of hyperthermophilic archaea. They are considered to be primordial enzymes of ATP synthesis in the early evolution of life. We present the first crystal structures, to our knowledge, of an ACD from the hyperthermophilic archaeon Candidatus Korachaeum cryptofilum. These structures reveal a unique arrangement of the ACD subunits alpha and beta within an α 2 β 2 -heterotetrameric complex. This arrangement significantly differs from other members of the superfamily. To transmit an activated phosphoryl moiety from the Ac-CoA binding site (within the alpha subunit) to the NDP-binding site (within the beta subunit), a distance of 51 Å has to be bridged. This transmission requires a larger rearrangement within the protein complex involving a 21-aa-long phosphohistidinecontaining segment of the alpha subunit. Spatial restraints of the interaction of this segment with the beta subunit explain the necessity for a second highly conserved His residue within the beta subunit. The data support the proposed four-step reaction mechanism of ACDs, coupling acyl-CoA thioesters with ATP synthesis. Furthermore, the determined crystal structure of the complex with bound Ac-CoA allows first insight, to our knowledge, into the determinants for acyl-CoA substrate specificity. The composition and size of loops protruding into the binding pocket of acyl-CoA are determined by the individual arrangement of the characteristic subdomains.X-ray structure | metabolic energy conversion | protein dynamics | acyl-coenzyme A thioester | superfamily N DP-forming acyl-CoA synthetases (ACDs) catalyze the conversion of acyl-CoA thioesters to the corresponding acids and couple this reaction with the synthesis of ATP via the mechanism of substrate-level phosphorylation. ACDs have been studied in detail in hyperthermophilic archaea, where they function as the major energy-conserving enzymes in the course of anaerobic sugar and peptide fermentation (1-4). It is believed that ACDs represent a primordial mechanism of ATP synthesis in the early evolution of life. ACDs were found in all acetate (acid)-forming archaea (5, 6) and in the eukaryotic parasitic protists Entamoeba histolytica (7) and Giardia lamblia (8), but they have not been found in acetate-forming bacteria. In bacteria, with the exception of Chloroflexus (9), the conversion of inorganic phosphate and the thioester acetyl (Ac)-CoA to acetate and ATP is catalyzed by two enzymes, phosphate Ac-transferase and acetate kinase (10).

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Acetyl-CoA Synthetase from the Amitochondriate EukaryoteGiardia lamblia Belongs to the Newly Recognized Superfamily of Acyl-CoA Synthetases (Nucleoside Diphosphate-forming)

Cited by 104 publications

References 40 publications

Molecular Characterization of a Heteromeric ATP-Citrate Lyase That Generates Cytosolic Acetyl-Coenzyme A in Arabidopsis,

Molecular Characterization of a Heteromeric ATP-Citrate Lyase That Generates Cytosolic Acetyl-Coenzyme A in Arabidopsis,

On the origins of cells: a hypothesis for the evolutionary transitions from abiotic geochemistry to chemoautotrophic prokaryotes, and from prokaryotes to nucleated cells

Structure of NDP-forming Acetyl-CoA synthetase ACD1 reveals a large rearrangement for phosphoryl transfer

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