A Simplified Method for Evaluating Chitin-Binding Activity Applied to YKL-40 (HC-gp39, CHI3L1) and Chitotriosidase

被引:0
|
作者
Suzuki, Keita [1 ]
Suzuki, Hidetoshi [1 ]
Tanaka, Ami [1 ]
Tanaka, Miwa [1 ]
Takase, Kairi [1 ]
Takei, Hiromu [1 ]
Kanaizumi, Tomoki [1 ]
Okawa, Kazuaki [1 ]
Bauer, Peter O. [2 ]
Oyama, Fumitaka [1 ]
机构
[1] Kogakuin Univ, Dept Chem & Life Sci, Tokyo 1920015, Japan
[2] Bioinova a s, Videnska 1083, Prague 14200, Czech Republic
来源
MOLECULES | 2025年 / 30卷 / 01期
基金
日本学术振兴会;
关键词
catalytic domain (CatD); chitin; chitin-binding activity; chitin-binding affinity assay; chitin-binding domain (CBD); chitotriosidase (CHIT1); chitinase-like proteins (CLPs); W69; residue; YKL-39; YKL-40; HUMAN CARTILAGE GP-39; SERUM YKL-40; CHITOOLIGOSACCHARIDE-BINDING; RHEUMATOID-ARTHRITIS; CARBOHYDRATE-BINDING; CRYSTAL-STRUCTURE; POTENTIAL MARKER; PROTEIN; IDENTIFICATION; EXPRESSION;
D O I
10.3390/molecules30010019
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
YKL-40 is structurally similar to chitotriosidase (CHIT1), an active chitinase, but it lacks chitin-degrading activity while retaining chitin-binding capability. Elevated YKL-40 levels are associated with inflammatory diseases and cancers, making it a valuable biomarker. We previously reported that the W69T substitution in YKL-40 significantly reduces its chitin-binding affinity, identifying W69 as a crucial binding site. In this study, we establish a novel chitin-binding affinity evaluation method using a three-step buffer system to assess the binding strength and specificity of chitin-binding proteins and apply it to characterize YKL-40's binding mechanism. Our findings confirm that YKL-40, through its key residue W69, exhibits highly specific and robust affinity to chitin. Unlike CHIT1, which has both a catalytic domain (CatD) and a chitin-binding domain (CBD) that allow for diverse binding and degradation activities, YKL-40 lacks a CBD and is specialized for specific chitin recognition without degrading it. Comparative analysis with YKL-39, which does not contain a corresponding W69 residue, highlights the unique role of this residue in YKL-40's chitin-binding activity that is potentially linked to immune and inflammatory responses. Our evaluation method clarifies YKL-40's binding properties and provides a versatile approach applicable to other chitin-binding proteins.
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页数:13
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