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

DOI: 10.1111/j.1742-4658.2011.08414.x DOI Help
PMID: 22059385 PMID Help

Authors: Geoffrey Masuyer (University of Bath) , Talat Jabeen (University of Bath) , Christopher T. Öberg (Lung University) , Hakon Leffler (Lund University) , Ulf J. Nilsson (Lund University) , Ravi Acharya (University of Bath)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Febs Journal

State: Published (Approved)
Published: November 2011

Open Access Open Access

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.

Journal Keywords: Crystallography; X-Ray; Cysteine; Databases; Protein; Dimerization; Drug; Galactosamine; Galactosides; Galectins; Humans; Hydrogen; Kinetics; Ligands; Models; Molecular; Phosphates; Protein; Recombinant; Thiogalactosides

Subject Areas: Biology and Bio-materials

Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography

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