1kjr
From Proteopedia
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| - | [[Image:1kjr.gif|left|200px]] | + | [[Image:1kjr.gif|left|200px]] |
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| - | '''Crystal Structure of the human galectin-3 CRD in complex with a 3'-derivative of N-Acetyllactosamine''' | + | {{Structure |
| + | |PDB= 1kjr |SIZE=350|CAPTION= <scene name='initialview01'>1kjr</scene>, resolution 1.55Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene> and <scene name='pdbligand=CL:CHLORIDE ION'>CL</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''Crystal Structure of the human galectin-3 CRD in complex with a 3'-derivative of N-Acetyllactosamine''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1KJR is a [ | + | 1KJR is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KJR OCA]. |
==Reference== | ==Reference== | ||
| - | 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 JM, Nilsson UJ, J Am Chem Soc. 2005 Feb 16;127(6):1737-43. PMID:[http:// | + | 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 JM, Nilsson UJ, J Am Chem Soc. 2005 Feb 16;127(6):1737-43. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15701008 15701008] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: all beta]] | [[Category: all beta]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:18:21 2008'' |
Revision as of 10:18, 20 March 2008
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| , resolution 1.55Å | |||||||
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| Ligands: | and | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of the human galectin-3 CRD in complex with a 3'-derivative of N-Acetyllactosamine
Overview
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.
About this Structure
1KJR is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 JM, Nilsson UJ, J Am Chem Soc. 2005 Feb 16;127(6):1737-43. PMID:15701008
Page seeded by OCA on Thu Mar 20 12:18:21 2008
Categories: Homo sapiens | Single protein | Arnoux, P. | Kahl-Knutsson, B. | Leffler, H. | Nilsson, U J. | Rini, J M. | Sorme, P. | CL | NAG | All beta
