3AAW

Mechanism of concerted inhibition of {alpha}2{beta}2-type heterooligomeric aspartate kinase from Corynebacterium glutamicum

(2010) J Biol Chem 285: 27477-27486

• PubMed: 20573952 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.1074/jbc.M110.111153
• Primary Citation of Related Structures:  
  3AAW, 3AB2, 3AB4


• PubMed Abstract: 
  

  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.

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Organizational Affiliation: 

Biotechnology Research Center, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.