The effect of carbohydrate binding modules and linkers on inhibitor binding to family 18 glycoside hydrolases
Peer reviewed, Journal article
Accepted version
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https://hdl.handle.net/11250/2734291Utgivelsesdato
2018Metadata
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Sammendrag
Enzyme catalyzed hydrolysis of glycosidic bonds is undertaken by glycoside hydrolases (GHs) in nature. In addition to a catalytic domain (CD), GHs often have carbohydrate-binding modules (CBMs) attached to the CD through a linker. Allosamidin binding to full-length GH18 Serratia marcescens ChiB and the catalytic domain only yield equal changes in reaction free energy (DGrº = -38 kJ/mol), enthalpy (DHrº = 18 kJ/mol), and entropy (-TDSrº = -57 kJ/mol).
Interestingly, the change in heat capacity (DCp,r) was 3-fold smaller for full-length vs. the CD alone (-263 vs. -695 J/K mol). Allosamidin binding to the full-length isoform and the CD alone of the GH18 human chitotriosidase yielded different DGrº (-46.9 vs. -38.9 kJ/mol) due to differences in DHrº (-58.2 vs. -50.2 kJ/mol), while -TDSrº and (11.3 vs. 11.3 kJ/mol) and DCp,r (-531 vs. -602 kJ/mol) are similar. The results combined show that the nature of the linker region and CBM affect the thermodynamic signatures of active site ligand binding.