3oyw

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Crystal structure of human galectin-1 in complex with thiodigalactoside

Structural highlights

3oyw is a 2 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 2.5Å
Ligands:CME, CSO, GAL, PRD_900027, YIO
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]

Publication Abstract from PubMed

High level galectin-1 expression results in cancer cell evasion of the immune response, increased tumour survival and aggressive metastases. Using a galectin-1 polyclonal antibody, high levels of galectin-1 protein were shown to be expressed by breast cancer cells established from FVB/N MMTV-c-neu mice as well as by the B16F10 melanoma cell line. In mixed lymphocyte cultures using tumour cells as antigenic stimulators, addition of recombinant galectin-1 dose-dependently inhibited lymphocyte production. Disaccharides were identified that inhibited galectin-1 function and increased growth and activation of CD8(+) CTL's killing cancer cells. X-ray crystallographic structures of human galectin-1 in complex with inhibitory disaccharides revealed their mode of binding. Combining galectin-blocking carbohydrates as adjuvants with vaccine immunotherapy in vivo to promote immune responses significantly decreased tumour progression and improved the outcomes for tumour challenged mice. This is the first report showing that suitably selected galectin-1 blocking disaccharides will act as adjuvants promoting vaccine stimulated immune responses against tumours in vivo.

Galectin inhibitory disaccharides promote tumour immunity in a breast cancer model.,Stannard KA, Collins PM, Ito K, Sullivan EM, Scott SA, Gabutero E, Darren Grice I, Low P, Nilsson UJ, Leffler H, Blanchard H, Ralph SJ Cancer Lett. 2010 Dec 28;299(2):95-110. Epub 2010 Sep 9. PMID:20826047[3]

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

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Citations
17 reviews cite this structure
Heusschen et al. (2013)
No citations found

See Also

References

  1. 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
  2. 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
  3. Stannard KA, Collins PM, Ito K, Sullivan EM, Scott SA, Gabutero E, Darren Grice I, Low P, Nilsson UJ, Leffler H, Blanchard H, Ralph SJ. Galectin inhibitory disaccharides promote tumour immunity in a breast cancer model. Cancer Lett. 2010 Dec 28;299(2):95-110. Epub 2010 Sep 9. PMID:20826047 doi:10.1016/j.canlet.2010.08.005

Contents


PDB ID 3oyw

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