Inhibition mechanism of human galectin-7 by a novel galactose-benzylphosphate inhibitor


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Abstract

Galectins are involved in many cellular processes due to their ability to bind carbohydrates. Understanding their functions has shown the necessity for potent and specific galectin inhibitors. Human galectin-7 (hGal-7), in particular, has been highlighted as an important marker in many types of cancer by either inhibiting or promoting tumour growth. Producing ligands able to selectively target hGal-7 will offer promising tools for deciphering cancer processes in which hGal-7 is involved as well as present potential solutions for future therapeutics. Here we report the high resolution crystal structure of hGal-7 in complex with a synthetic 2-O-benzylphosphate-galactoside inhibitor (which is > 60-fold more potent than its parent galactoside). The high resolution crystallographic analysis highlights the validity of using saccharide derivatives, conserving properties of the galactose binding, while enhanced affinity and specificity is provided by the added phosphate group. This structural information will allow the design of further inhibitors with improved potency and specificity.DatabaseThe atomic coordinates for the complex of human galectin-7 as well as for the free structure have been deposited with the Protein Data Bank (accession numbers 3ZXE and 3ZXF respectively)Structured digital abstracthGal-7 and hGal-7 bind by X-ray crystallography (View interaction)Human galectin-7 (hGal-7) has been highlighted as an important marker in many types of cancer. Producing ligands able to selectively target hGal-7 will offer promising tools for deciphering cancer processes in which hGal-7 is involved, as well as present potential solutions for future therapeutics. Here we report the high resolution crystal structure of hGal-7 in complex with a synthetic 2-O-benzylphosphate-galactoside inhibitor.

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