Mechanism of Concerted Inhibition of alpha(2)beta(2)-type Hetero-oligomeric Aspartate Kinase from Corynebacterium glutamicum

作者：Yoshida Ayako; Tomita Takeo; Kuzuyama Tomohisa; Nishiyama Makoto^*

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285(35): 27477-27486.

DOI：10.1074/jbc.M110.111153

Aspartate kinase (AK) is the first and committed enzyme of the biosynthetic pathway producing aspartate family amino acids, lysine, threonine, and methionine. AK from Corynebacterium glutamicum (CgAK), a bacterium used for industrial fermentation of amino acids, including glutamate and lysine, is inhibited by lysine and threonine in a concerted manner. To elucidate the mechanism of this unique regulation in CgAK, we determined the crystal structures in several forms: an inhibitory form complexed with both lysine and threonine, an active form complexed with only threonine, and a feedback inhibition-resistant mutant (S301F) complexed with both lysine and threonine. CgAK has a characteristic alpha(2)beta(2)-type heterotetrameric structure made up of two alpha subunits and two beta subunits. Comparison of the crystal structures between inhibitory and active forms revealed that binding inhibitors causes a conformational change to a closed inhibitory form, and the interaction between the catalytic domain in the alpha subunit and beta subunit (regulatory subunit) is a key event for stabilizing the inhibitory form. This study shows not only the first crystal structures of alpha(2)beta(2)-type AK but also the mechanism of concerted inhibition in CgAK.

• 出版日期2010-8-27