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

Proceedings of the National Academy of Sciences of the United States of America
Renato H-J WeißeAxel J Scheidig

Abstract

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 α2β2-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 phosphohistidine-containing 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 th...Continue Reading

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Citations

Aug 5, 2017·Acta Crystallographica. Section D, Structural Biology·Jinhong HuMarie E Fraser
Jul 10, 2019·Acta Crystallographica. Section D, Structural Biology·Ji HuangMarie E Fraser
Jul 7, 2020·Acta Crystallographica. Section F, Structural Biology Communications·Ji Huang, Marie E Fraser
Jul 14, 2020·Frontiers in Microbiology·William F Martin
Aug 5, 2016·Acta Crystallographica. Section D, Structural Biology·Ji Huang, Marie E Fraser
Aug 15, 2019·Protein Science : a Publication of the Protein Society·Vinh H NguyenMarie E Fraser
Mar 23, 2019·Nature Microbiology·Joana C Xavier, William F Martin
Jan 22, 2021·FEMS Microbiology Reviews·April M LewisRobert M Kelly
Mar 2, 2021·Acta Crystallographica. Section D, Structural Biology·Ji Huang, Marie E Fraser
Feb 10, 2021·Journal of Bacteriology·Tom KupratPeter Schönheit

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