Work

Heparin-binding of the human chitinase-like protein YKL-40 is allosterically modified by chitin oligosaccharides

Year: 2024

Type: article

Abstract: The chitinase-like protein YKL-40 (CHI3L1) has been implicated in the pathophysiology of inflammation and cancer. Recent studies highlight the growing interest in targeting and blocking the activity of YKL-40 to treat cancer. Some of those targeting-strategies have been developed to directly block the heparin-affinity of YKL-40 with promising results. This study explores how short chain chitooligosaccharides (ChOS) affect the heparin-binding affinity of YKL-40. Our findings reveal that ChOS act as allosteric effectors, decreasing the heparin-binding affinity of YKL-40 in a size- and dose-dependent manner. Our results provide insights into the heparin affinity of YKL-40 and how ChOS can be used to target the heparin activity of YKL-40 in diseases. Since ChOS has many beneficial properties, such as being non-toxic and biodegradable, these results provide intriguing opportunities for applying them as allosteric effectors of the heparin-binding affinity of YKL-40. • Chitin oligosaccharides A 4 , A 5 , and A 6 bind to YKL-40 with micromolar affinity. • Chitin oligosaccharides A 4 , A 5 , A 6 , and chitooligosaccharides (ChOS) allosterically decrease the heparin affinity of YKL-40. • Rotation of the Trp99 sidechain out of the chitin-binding site is the crucial factor for decreased heparin affinity of YKL-40.

Source: Biochemistry and Biophysics Reports

DOI: 10.1016/j.bbrep.2024.101908