Evolutionary insights into sequence modifications governing chitin recognition and chitinase inactivity in YKL-40 (HC-gp39, CHI3L1).

ABSTRACT: YKL-40, also known as human cartilage glycoprotein-39 (HC-gp39) or CHI3L1, shares structural similarities with chitotriosidase (CHIT1), an active chitinase, but lacks chitinase activity. Despite being a biomarker for inflammatory disorders and cancer, the reasons for YKL-40's inert chitinase function have remained elusive. This study reveals that the loss of chitinase activity in YKL-40 has risen from multiple sequence modifications influencing its chitin affinity. Contrary to the common belief associating the lack of chitinase activity with amino acid substitutions in the catalytic motif, attempts to activate YKL-40 by creating two amino acid mutations in the catalytic motif (MT-YKL-40) proved ineffective. Subsequent exploration that included creating chimeras of MT-YKL-40 and CHIT1 catal

SUBMITTER: Suzuki K 

PROVIDER: S-EPMC11190707 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature