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Involvement of subdomain II in the recognition of acetyl‐CoA revealed by the crystal structure of homocitrate synthase from Sulfolobus acidocaldarius
Author(s) -
Suzuki Tomohiro,
Tomita Takeo,
Hirayama Kenta,
Suzuki Michio,
Kuzuyama Tomohisa,
Nishiyama Makoto
Publication year - 2021
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15527
Subject(s) - sulfolobus acidocaldarius , protein data bank (rcsb pdb) , sulfolobus , atp synthase , domain (mathematical analysis) , lysine , chemistry , transferase , archaea , stereochemistry , biochemistry , enzyme , amino acid , gene , mathematical analysis , mathematics
Homocitrate synthase (HCS) catalyzes the aldol condensation of α‐ketoglutarate and acetyl coenzyme A to form homocitrate, which is the first committed step of lysine biosynthesis through the α‐aminoadipate pathway in yeast, fungi, and some prokaryotes. We determined the crystal structure of a truncated form of HCS from a hyperthermophilic acidophilic archaeon, Sulfolobus acidocaldarius , which lacks the RAM ( R egulation of a mino acid m etabolism) domain at the C terminus serving as the regulatory domain for the feedback inhibition by lysine, in complex with α‐ketoglutarate, Mg 2+ , and CoA. This structure coupled with mutational analysis revealed that a subdomain, subdomain II, connecting the N‐terminal catalytic domain and C‐terminal RAM domain is involved in the recognition of acetyl‐CoA. This is the first structural evidence of the function of subdomain II in the related enzyme family, which will lead to a better understanding of the catalytic mechanism of HCS. Databases Structural data are available in the RCSB PDB database under the accession number 6KTQ .