| Structural highlights
Function
[LEG3_HUMAN] Galactose-specific lectin which binds IgE. May mediate with the alpha-3, beta-1 integrin the stimulation by CSPG4 of endothelial cells migration. Together with DMBT1, required for terminal differentiation of columnar epithelial cells during early embryogenesis (By similarity). In the nucleus: acts as a pre-mRNA splicing factor. Involved in acute inflammatory responses including neutrophil activation and adhesion, chemoattraction of monocytes macrophages, opsonization of apoptotic neutrophils, and activation of mast cells.[1] [2] [3]
Publication Abstract from PubMed
Carbohydrate recognition by proteins is a fundamental aspect of communication within and between living cells. Understanding the molecular basis of carbohydrate-protein interactions is a prerequisite for rational design of synthetic ligands. Here we report the high- to ultra-high resolution crystal structures of the carbohydrate-recognition domain of galectin-3 (Gal3C) in the ligand-free state (1.08 A at 100 K, 1.25 A at 298 K) and in complex with lactose (0.86 A) or glycerol (0.9 A). These structures reveal striking similarities in the positions of water and carbohydrate oxygen atoms in all three states, indicating that the binding site of Gal3C is preorganized to coordinate oxygen atoms in an arrangement near-optimal for recognition of beta-galactosides. Deuterium NMR relaxation dispersion experiments and molecular dynamics simulations demonstrate that all water molecules in the lactose binding site exchange with bulk water on a time scale of nanoseconds, or less. Nevertheless, molecular dynamics simulations identify transient water binding at sites that agree well with those observed by crystallography, indicating that the energy landscape of the binding site is maintained in solution. All heavy atoms of glycerol are positioned identically to the corresponding ones of lactose in the Gal3C complexes. However, glycerol binding to Gal3C is insignificant in solution at room temperature, as monitored by NMR spectroscopy or isothermal titration calorimetry under conditions where lactose binding is readily detected. These observations make a case for protein cryo-crystallography as a valuable screening method in fragment-based drug discovery, and further suggest that identification of water sites might inform inhibitor design.
The carbohydrate-binding site in galectin-3 is pre-organized to recognize a sugar-like framework of oxygens: ultra-high resolution structures and water dynamics.,Saraboji K, Hakansson M, Genheden S, Diehl C, Qvist J, Weininger U, Nilsson UJ, Leffler H, Ryde U, Akke M, Logan DT Biochemistry. 2011 Nov 23. PMID:22111949[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fukushi J, Makagiansar IT, Stallcup WB. NG2 proteoglycan promotes endothelial cell motility and angiogenesis via engagement of galectin-3 and alpha3beta1 integrin. Mol Biol Cell. 2004 Aug;15(8):3580-90. Epub 2004 Jun 4. PMID:15181153 doi:http://dx.doi.org/10.1091/mbc.E04-03-0236
- ↑ Henderson NC, Sethi T. The regulation of inflammation by galectin-3. Immunol Rev. 2009 Jul;230(1):160-71. doi: 10.1111/j.1600-065X.2009.00794.x. PMID:19594635 doi:10.1111/j.1600-065X.2009.00794.x
- ↑ Haudek KC, Spronk KJ, Voss PG, Patterson RJ, Wang JL, Arnoys EJ. Dynamics of galectin-3 in the nucleus and cytoplasm. Biochim Biophys Acta. 2010 Feb;1800(2):181-189. Epub 2009 Jul 16. PMID:19616076 doi:S0304-4165(09)00194-9
- ↑ Saraboji K, Hakansson M, Genheden S, Diehl C, Qvist J, Weininger U, Nilsson UJ, Leffler H, Ryde U, Akke M, Logan DT. The carbohydrate-binding site in galectin-3 is pre-organized to recognize a sugar-like framework of oxygens: ultra-high resolution structures and water dynamics. Biochemistry. 2011 Nov 23. PMID:22111949 doi:10.1021/bi201459p
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