Computational insights into the substrate recognition mechanism of cartilage extracellular matrix degradation.

ABSTRACT: Articular cartilage is connective tissue that forms a slippery load-bearing joint surface between bones. With outstanding mechanical properties, it plays an essential role in cushioning impact and protecting the ends of bones. Abnormal mechanical stimulation, such as repetitive overloading or chondral injury, induces excessive cartilage extracellular matrix (ECM) degradation, leading to osteoarthritis and other joint disorders. A disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5) is an aggrecanase that dominates the catalysis of aggrecan, the major proteoglycan in the cartilage ECM. Intriguingly, unlike its critical cleavage site Glu³⁷³-³⁷⁴Ala, another potential cleavage site, Glu⁴¹⁹-⁴²⁰Ala, composed of the same amino acids

SUBMITTER: Lai YY 

PROVIDER: S-EPMC8526910 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature