Elucidation of the Catalytic Apparatus and Mechanism of Human Chitotriosidase‑1.

ABSTRACT: Despite extensive research over the past three decades, the catalytic mechanism of human chitotriosidase-1 (hCHIT1) has remained incompletely understood. To address this gap, we reanalyzed all available structural information and, integrating experimental data with multiscale molecular simulations, successfully modeled the full-length structure of hCHIT1 for the first time, including the previously unresolved proline-rich linker essential for domain communication. This comprehensive model enabled us to propose a general mechanism of hCHIT1 catalysis and to elucidate the distinct functional roles of all four highly conserved structural motifs of the glycoside hydrolase 18 (GH18) family, a group comprising over 65,000 known members across all domains of life. We further investigated the infl

SUBMITTER: Niedzialek D 

PROVIDER: S-EPMC12502790 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature