6ktq

Publication Abstract from PubMed

Homocitrate synthase (HCS) catalyzes the aldol condensation of alpha-ketoglutarate and acetyl coenzyme A to form homocitrate, which is the first committed step of lysine biosynthesis through the alpha-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 (Regulation of amino acid metabolism) domain at the C terminus serving as the regulatory domain for the feedback inhibition by lysine, in complex with alpha-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.

Involvement of subdomain II in the recognition of acetyl-CoA revealed by the crystal structure of homocitrate synthase from Sulfolobus acidocaldarius.,Suzuki T, Tomita T, Hirayama K, Suzuki M, Kuzuyama T, Nishiyama M FEBS J. 2020 Sep 8. doi: 10.1111/febs.15527. PMID:32897601^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.