Опубликована: Март 14, 2024

Coenzyme Q (CoQ) is a lipidic compound widely distributed in nature with crucial functions metabolism, protection against oxidative damage and ferroptosis, other processes. CoQ biosynthesis conserved complex pathway involving several proteins. COQ2 member of the UbiA family transmembrane prenyltransferases that catalyzes condensation head tail precursors CoQ, key step process because its product first intermediate will be modified by next component synthesis process. Mutations this protein have been linked to primary deficiency humans, rare disease predominantly affecting organs high energy demand. The reaction catalyzed mechanism are still unknown. Here we aimed at clarifying exploring possible substrate binding sites using strategy based on homology, comprising identification ligand-bound homologs solved structures available Protein Data Bank (PDB) their subsequent structural superposition AlphaFold predicted model for COQ2. results highlight some residues located central cavity or matrix loops may involved interaction, them mutated patients. Furthermore, analyze modifications introduced pathogenic mutations found humans. These findings shed new light understanding function and, thus, pathogenicity deficiency.

Язык: Английский