Structural highlights
1w6n is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , |
| NonStd Res: | |
| Related: | 1gzw, 1w6m, 1w6o, 1w6p, 1w6q |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[LEG1_HUMAN] May regulate apoptosis, cell proliferation and cell differentiation. Binds beta-galactoside and a wide array of complex carbohydrates. Inhibits CD45 protein phosphatase activity and therefore the dephosphorylation of Lyn kinase.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Human galectin-1 is a potent multifunctional effector that participates in specific protein-carbohydrate and protein-protein (lipid) interactions. By determining its X-ray structure, we provide the basis to define the structure of its ligand-binding pocket and to perform rational drug design. We have also analysed whether single-site mutations introduced at some distance from the carbohydrate recognition domain can affect the lectin fold and influence sugar binding. Both the substitutions introduced in the C2S and R111H mutants altered the presentation of the loop, harbouring Asp123 in the common "jelly-roll" fold. The orientation of the side-chain was inverted 180 degrees and the positions of two key residues in the sugar-binding site of the R111H mutant were notably shifted, i.e. His52 and Trp68. Titration calorimetry was used to define the decrease in ligand affinity in both mutants and a significant increase in the entropic penalty was found to outweigh a slight enhancement of the enthalpic contribution. The position of the SH-groups in the galectin appeared to considerably restrict the potential to form intramolecular disulphide bridges and was assumed to be the reason for the unstable lectin activity in the absence of reducing agent. However, this offers no obvious explanation for the improved stability of the C2S mutant under oxidative conditions. The noted long-range effects in single-site mutants are relevant for the functional divergence of closely related galectins and in more general terms, the functionality definition of distinct amino acids.
Growth-regulatory human galectin-1: crystallographic characterisation of the structural changes induced by single-site mutations and their impact on the thermodynamics of ligand binding.,Lopez-Lucendo MF, Solis D, Andre S, Hirabayashi J, Kasai K, Kaltner H, Gabius HJ, Romero A J Mol Biol. 2004 Oct 29;343(4):957-70. PMID:15476813[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ He J, Baum LG. Presentation of galectin-1 by extracellular matrix triggers T cell death. J Biol Chem. 2004 Feb 6;279(6):4705-12. Epub 2003 Nov 14. PMID:14617626 doi:10.1074/jbc.M311183200
- ↑ Nishi N, Abe A, Iwaki J, Yoshida H, Itoh A, Shoji H, Kamitori S, Hirabayashi J, Nakamura T. Functional and structural bases of a cysteine-less mutant as a long-lasting substitute for galectin-1. Glycobiology. 2008 Dec;18(12):1065-73. Epub 2008 Sep 16. PMID:18796645 doi:10.1093/glycob/cwn089
- ↑ Lopez-Lucendo MF, Solis D, Andre S, Hirabayashi J, Kasai K, Kaltner H, Gabius HJ, Romero A. Growth-regulatory human galectin-1: crystallographic characterisation of the structural changes induced by single-site mutations and their impact on the thermodynamics of ligand binding. J Mol Biol. 2004 Oct 29;343(4):957-70. PMID:15476813 doi:http://dx.doi.org/10.1016/j.jmb.2004.08.078
