Catalytic mechanism study of ATP-citrate lyase during citryl-CoA synthesis process.

ABSTRACT: ATP-citrate lyase (ACLY) is a critical metabolic enzyme and promising target for drug development. The structure determinations of ACLY have revealed its homotetramer states with various subunit symmetries, but catalytic mechanism of ACLY tetramer and the importance of subunit symmetry have not been clarified. Here, we constructed the free energy landscape of ACLY tetramer with arbitrary subunit symmetries and investigated energetic and conformational coupling of subunits during citryl-CoA synthesis process. The optimal conformational pathway indicates that ACLY tetramer encounters three critical conformational barriers and undergoes a loss of rigid-D2 symmetry to gain an energetic advantage. Energetic coupling of conformational changes and biochemical reactions suggests that these biologi

SUBMITTER: Shi D 

PROVIDER: S-EPMC11365397 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature