Characterization of Ten Heterotetrameric NDP-Dependent Acyl-CoA Synthetases of the Hyperthermophilic Archaeon<i>Pyrococcus furiosus</i>

Scott, Joseph W.; Poole, Farris L.; Adams, Michael W. W.

doi:10.1155/2014/176863

Cited by 12 publications

(16 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1B). The alpha subunit comprises three subdomains (1-2-5), and the beta subunit comprises two subdomains (3)(4). The numbering is according to the nomenclature established for ecSCS (12,19,20) (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…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)(2)(3)(4). It is believed that ACDs represent a primordial mechanism of ATP synthesis in the early evolution of life.…”

mentioning

confidence: 99%

“…The necessity for a four-step mechanism may originate from a shortening of the proposed swinging loop, which facilitates the phosphoryl transfer between the subunits (20). However, due to the completely different arrangement of the subdomains within ACD [alpha(1-2-5)/beta (3)(4)] in comparison to ecSCS [alpha(1-2)/beta(3-4-5)], a different 3D arrangement of Significance Acyl-CoA thioesters are key substrates for energy conversion. Related ATP/GTP-producing synthetases form a large superfamily with members in all kingdoms of life.…”

mentioning

confidence: 99%

“…ACDs are versatile enzymes that are capable of metabolizing a variety of CoA thioesters generated in the course of sugar and peptide fermentation (3,4,21). In contrast, the ecSCS specifically binds succinyl-CoA, accepting only small aliphatic CoA thioesters as additional substrates (22).…”

mentioning

confidence: 99%

“…The ACLY is even more specific for Ac-CoA (23). Because ACDs are involved in sugar and amino acid metabolism, they are ambivalent regarding their converted substrates (3,4,24,25). In addition, domain shuffling creates a very diverse pattern of subdomain organization within members of the ACD family (8).…”

mentioning

confidence: 99%

See 4 more Smart Citations

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.

View full text Add to dashboard Cite

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).

show abstract