Premium
Inhibition mechanism of human galectin‐7 by a novel galactose‐benzylphosphate inhibitor
Author(s) -
Masuyer Geoffrey,
Jabeen Talat,
Öberg Christopher T.,
Leffler Hakon,
Nilsson Ulf J.,
Acharya K. Ravi
Publication year - 2012
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2011.08414.x
Subject(s) - galectin , galactose , galectin 1 , galactoside , chemistry , high resolution , biochemistry , computational biology , galactosides , biology , microbiology and biotechnology , enzyme , remote sensing , geology
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. Database
The 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 abstract• hGal‐7 and hGal‐7 bind by X‐raycrystallography ( Viewinteraction )