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Molecular architecture of OXGR1 reveals an evolutionary conserved mechanisms for metabolite surveillance - PubMed

4 hours ago
  • #GPCR
  • #Structural Biology
  • #Metabolite Sensing
  • OXGR1 is a GPCR that senses metabolites like α-ketoglutarate and itaconate from the TCA cycle.
  • Cryo-EM structures reveal a positively charged binding pocket with a hydrogen-bond network for selective dicarboxylic acid recognition.
  • Hydrophobic residue arrangements modulate ligand potency and selectivity, and noncanonical motifs like FRY are essential for activation.
  • Evolutionary analyses show conserved mechanisms, highlighting OXGR1's role in metabolic homeostasis and potential therapeutic applications.