ACT domains of the lysine-sensitive aspartokinase isoenzyme AKII of Bacillus subtilis (BS) strain 168 and related proteins
This CD includes the N-terminal of the two ACT domains of the lysine-sensitive aspartokinase isoenzyme AKII of Bacillus subtilis (BS) strain 168, and the lysine plus threonine-sensitive aspartokinase of Corynebacterium glutamicum, and related sequences. In B. subtilis 168, the regulation of the diaminopimelate (Dap)-lysine biosynthetic pathway involves dual control by Dap and lysine, effected through separate Dap- and lysine-sensitive aspartokinase isoenzymes. The B. subtilis 168 AKII is induced by methionine and repressed and inhibited by lysine. Although Corynebacterium glutamicum is known to contain a single aspartokinase, both the succinylase and dehydrogenase variant pathways of DAP-lysine synthesis operate simultaneously in this organism. In corynebacteria and other various Gram-positive bacteria, the DAP-lysine pathway is feedback regulated by the concerted action of lysine and threonine. Conserved residues in the ACT domains have been shown to be involved in this concerted feedback inhibition. Also included in this CD are the aspartokinases of the extreme thermophile, Thermus thermophilus HB27, the Gram-negative obligate methylotroph, Methylophilus methylotrophus AS1, and those single aspartokinases found in Pseudomonas aeruginosa, C. glutamicum, and Amycolatopsis lactamdurans. B. subtilis 168 AKII, and the C. glutamicum, Streptomyces clavuligerus and A. lactamdurans aspartokinases are described as tetramers consisting of two alpha and two beta subunits; the alpha (44 kD) and beta (18 kD) subunits formed by two in-phase overlapping polypeptides. This CD includes the first ACT domain C-terminal to the AK catalytic domain of the alpha subunit and the first ACT domain of the beta subunit that lacks the AK catalytic domain. Unlike the C. glutamicum AK beta subunit, which is involved in feedback regulation, the B. subtilis AKII beta subunit is not. Cyanobacteria aspartokinases are unique to this CD and they have a unique domain architecture with two tandem pairs of ACT domains, C-terminal to the catalytic AK domain. In this CD, the first and third cyanobacteria AK ACT domains are present. Members of this CD belong to the superfamily of ACT regulatory domains.
Comment:Mutation of Ser301 (in this ACT domain 1) and Gly345 (in ACT domain 2) were shown to be involved in the concerted feedback inhibition of lysine and threonine of the Corynebacterium glutamicum aspartokinase.