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  current news   Press   selected story    
     
  24 February 2015  
 
Structural and Thermodynamic Insights into Chitooligosaccharide Binding to Human Cartilage Chitinase 3-Like Protein 2 (CHI3L2 or YKL-39)
 
 




Authors
Araya Ranok1, Jantana Wongsantichon2, Robert C. Robinson2,3,*, and Wipa Suginta1,*

1  Biochemistry-Electrochemistry Research Unit, Schools of Chemistry and Biochemistry, Institute of    Science, Suranaree University of Technology, Nakhon Ratchasima, Thailand
2  Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR),    Biopolis, Singapore
3  Department of Biochemistry, National University of Singapore, 8 Medical Drive, Singapore 117597

Published online ahead of print in JBC on 4 December 2014.

Abstract
Four crystal structures of human YKL-39 were solved in the absence and presence of chitooligosaccharides. The structure of YKL-39 comprises a major (β/α)8 TIM barrel domain and a small α+β insertion domain. Structural analysis demonstrates that YKL-39 interacts with chitooligosaccharides through hydrogen bonds and hydrophobic interactions. The binding of chitin fragments induces local conformational changes that facilitate tight binding. Compared with other GH-18 members, YKL-39 has the least extended chitin-binding cleft, containing five subsites for sugars, namely (-3)(-2)(-1)(+1)(+2), with Trp360 playing a prominent role in the sugar-protein interactions at the centre of the chitin-binding cleft. Evaluation of binding affinities obtained from isothermal titration calorimetry and intrinsic fluorescence spectroscopy suggests that YKL-39 binds to chitooligosaccharides with Kd values in the micromolar concentration range and that the binding energies increase with the chain length. There were no significant differences between the Kd values of chitopentaose and chitohexaose, supporting the structural evidence for the five-binding subsite topology. Thermodynamic analysis indicates that binding of chitooligosaccharide to YKL-39 is mainly driven by enthalpy.

Figure:

Figure Legend: Phenotypic characterization of miR-1000 mutants.

Surface representation and of the sugar-binding cleft of YKL-39, showing chitohexaose occupying subsites -3 to +3. The interaction at subsite +3 appears weak. Trp36 is highlighted in dark blue and Tyr234 is labeled.


For more information on Robert ROBINSON's laboratory, please click here.