9obo | pdb_00009obo
Crystal structure of Mycobacterium tuberculosis isocitrate lyase 2 fixed in the apo form with disulfide bonds
Structural highlights
FunctionACEA2_MYCTO Involved in the persistence and virulence of M.tuberculosis. Catalyzes the reversible formation of succinate and glyoxylate from isocitrate, a key step of the glyoxylate cycle, which operates as an anaplerotic route for replenishing the tricarboxylic acid cycle during growth on fatty acid substrates.[1] [2] [3] Publication Abstract from PubMedMycobacterium tuberculosis isocitrate lyase 2 (ICL2) is an allosterically regulated enzyme required for growth on non-glycolytic carbon substrates during infection. Although acetyl-CoA and its analogues are known to activate ICL2, the molecular basis of this regulation has remained unclear. Here, we combine protein NMR, crystallography, molecular dynamics, and mutagenesis to show that two structural features unique to ICL2, the C-terminal domain and a helical substructure in the N-terminal catalytic domain, govern its allostery. Acetyl-CoA binding promotes dimerisation of the C-terminal domain and disrupts its contacts with the helical substructure to trigger conformational changes that activate the enzyme. Together, these findings reveal how a non-substrate metabolite drives isocitrate lyase activation, uncovering the allosteric mechanism that controls M. tuberculosis metabolism and informs new therapeutic strategies. Structural basis of allosteric activation of Mycobacterium tuberculosis isocitrate lyase 2.,Huang EY, Kwai BXC, Jiao W, Taka J, Wilde KL, Sethi A, Maher MJ, Bashiri G, Leung IKH Commun Biol. 2026 Mar 9. doi: 10.1038/s42003-026-09821-6. PMID:41803459[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
