1KJL

High Resolution X-Ray Structure of Human Galectin-3 in complex with LacNAc


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.187 

wwPDB Validation   3D Report Full Report


This is version 2.1 of the entry. See complete history


Literature

Structural and thermodynamic studies on cation-Pi interactions in lectin-ligand complexes: high-affinity galectin-3 inhibitors through fine-tuning of an arginine-arene interaction.

Sorme, P.Arnoux, P.Kahl-Knutsson, B.Leffler, H.Rini, J.M.Nilsson, U.J.

(2005) J Am Chem Soc 127: 1737-1743

  • DOI: https://doi.org/10.1021/ja043475p
  • Primary Citation of Related Structures:  
    1KJL, 1KJR

  • PubMed Abstract: 

    The high-resolution X-ray crystal structures of the carbohydrate recognition domain of human galectin-3 were solved in complex with N-acetyllactosamine (LacNAc) and the high-affinity inhibitor, methyl 2-acetamido-2-deoxy-4-O-(3-deoxy-3-[4-methoxy-2,3,5,6-tetrafluorobenzamido]-beta-D-galactopyranose)-beta-D-glucopyranoside, to gain insight into the basis for the affinity-enhancing effect of the 4-methoxy-2,3,5,6-tetrafluorobenzamido moiety. The structures show that the side chain of Arg144 stacks against the aromatic moiety of the inhibitor, an interaction made possible by a reorientation of the side chain relative to that seen in the LacNAc complex. Based on these structures, synthesis of second generation LacNAc derivatives carrying aromatic amides at 3'-C, followed by screening with a novel fluorescence polarization assay, has led to the identification of inhibitors with further enhanced affinity for galectin-3 (K(d) > or = 320 nM). The thermodynamic parameters describing the binding of the galectin-3 C-terminal to selected inhibitors were determined by isothermal titration calorimetry and showed that the affinity enhancements were due to favorable enthalpic contributions. These enhancements could be rationalized by the combined effects of the inhibitor aromatic structure on a cation-Pi interaction and of direct interactions between the aromatic substituents and the protein. The results demonstrate that protein-ligand interactions can be significantly enhanced by the fine-tuning of arginine-arene interactions.


  • Organizational Affiliation

    Organic and Bioorganic Chemistry, Lund University, P. O. Box 124, SE-221 00 Lund, Sweden.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Galectin-3146Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P17931 (Homo sapiens)
Explore P17931 
Go to UniProtKB:  P17931
PHAROS:  P17931
GTEx:  ENSG00000131981 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP17931
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
B
2N/A
Glycosylation Resources
GlyTouCan:  G00055MO
GlyCosmos:  G00055MO
GlyGen:  G00055MO
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.187 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 37.6α = 90
b = 58.4β = 90
c = 64γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
SOLVEphasing
CNSrefinement

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-04-12
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2023-08-16
    Changes: Data collection, Database references, Refinement description, Structure summary