Catalytic Reaction Mechanism of Bacterial GH92 α-1,2-Mannosidase: A QM/MM Metadynamics Study


ChemPhysChem, vol.24, no.24, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 24 Issue: 24
  • Publication Date: 2023
  • Doi Number: 10.1002/cphc.202300628
  • Journal Name: ChemPhysChem
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, PASCAL, Biotechnology Research Abstracts, Chemical Abstracts Core, Chimica, Compendex, EMBASE, INSPEC, MEDLINE
  • Keywords: alpha-mannosidase, catalysis, glycoside hydrolase 92, lysosomal storage disease, QM/MM metadynamics
  • Hacettepe University Affiliated: Yes


The catalytic mechanism of a (Formula presented.) -dependent family 92 (Formula presented.) -mannosidase, which is abundantly present in human gut flora and malfunctions leading to the lysosomal storage disease α-mannosidosis, has been investigated using quantum mechanics/molecular mechanics and metadynamics methods. Computational efforts show that the enzyme follows a conformational itinerary of, and the (Formula presented.) ion serves a dual purpose, as it not only distorts the sugar ring but also plays a crucial role in orchestrating the arrangement of catalytic residues. This orchestration, in turn, contributes to the facilitation of (Formula presented.) conformers for the ensuing reaction. This mechanistic insight is well-aligned with the experimental predictions of the catalytic pathway, and the computed energies are of the same order of magnitude as the experimental estimations. Hence, our results extend the mechanistic understanding of glycosidases.