We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

6b8k

From Proteopedia

Jump to: navigation, search

Crystal structure of Human galectin-3 CRD in complex with Lactulose

Structural highlights

6b8k is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.28Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

Galectins are carbohydrate binding proteins (lectins), which characteristically bind beta-galactosides. Galectins play a role in tumour progression through involvement in proliferation, metastasis, angiogenesis, immune evasion and drug resistance. There is need for inhibitors (antagonists) that are specific for distinct galectins and that can interfere with galectin-carbohydrate interactions during cancer progression. Here, we propose that lactulose, a non-digestible galactose-fructose disaccharide, presents a novel inhibitor scaffold for design of inhibitors against galectins. Thermodynamic evaluation displays binding affinity of lactulose against the galectin-1 and galectin-3 carbohydrate recognition domain (CRD). Crystal structures of galectin-1 and galectin-3 in complex with lactulose reveal for the first time the molecular basis of the galectin-lactulose interactions. Molecular modelling was implemented to propose novel lactulose derivatives as potent anti-cancer agents.

Lactulose as a novel template for anticancer drug development targeting galectins.,Kishor C, Ross RL, Blanchard H Chem Biol Drug Des. 2018 Oct;92(4):1801-1808. doi: 10.1111/cbdd.13348. Epub 2018 , Jul 1. PMID:29888844^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Kishor C, Ross RL, Blanchard H. Lactulose as a novel template for anticancer drug development targeting galectins. Chem Biol Drug Des. 2018 Oct;92(4):1801-1808. doi: 10.1111/cbdd.13348. Epub 2018 , Jul 1. PMID:29888844 doi:http://dx.doi.org/10.1111/cbdd.13348