4r9a

From Proteopedia

(Difference between revisions)

Revision as of 17:17, 18 January 2017

Crystal structure of Human galectin-3 CRD in complex with lactose (pH 7.0, PEG4000)

Structural highlights

4r9a is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	4r9b, 4r9c, 4r9d, 4rl7
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

Galectin-3 (Gal-3) which shows affinity of beta-galactosides is a cancer-related protein. Thus, it is important to understand its ligand binding mechanism and then design its specific inhibitor. It was suggested that the positions of water molecules in Gal-3 ligand-binding site could be replaced by appropriate chemical groups of ideal inhibitors. However, the reported structures of Gal-3 carbohydrate recognition domain (CRD) complexed with lactose showed that the number of water molecules are different and the water positions are inconsistent in the ligand-binding site. This study reported four high-resolution (1.24-1.19 A) structures of Gal-3 CRD complexed with lactose, and accurately located 12 conserved water molecules in the water network of Gal-3 CRD ligand-binding site by merging these structures. These water molecules either directly stabilize the binding of Gal-3 CRD and lactose, or hold the former water molecules at the right place. In particular, water molecule 4 (W4) which only coordinates with water molecule 5 (W5) and water molecule 6 (W6) plays a key role in stabilizing galactose residue. In addition, by three-dimensional alignment of the positions of all residues, 14 flexible parts of Gal-3 CRD were found to dynamically fluctuate in the crystalline environment.

The water network in galectin-3 ligand binding site guides inhibitor design.,Su J, Zhang T, Wang P, Liu F, Tai G, Zhou Y Acta Biochim Biophys Sin (Shanghai). 2015 Mar;47(3):192-8. doi:, 10.1093/abbs/gmu132. Epub 2015 Feb 5. PMID:25662390^[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
↑ Su J, Zhang T, Wang P, Liu F, Tai G, Zhou Y. The water network in galectin-3 ligand binding site guides inhibitor design. Acta Biochim Biophys Sin (Shanghai). 2015 Mar;47(3):192-8. doi:, 10.1093/abbs/gmu132. Epub 2015 Feb 5. PMID:25662390 doi:http://dx.doi.org/10.1093/abbs/gmu132

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4r9a"

Categories: Su, J Y | Sugar binding protein

@@ Line 1: / Line 1: @@
 ==Crystal structure of Human galectin-3 CRD in complex with lactose (pH 7.0, PEG4000)==
 <StructureSection load='4r9a' size='340' side='right' caption='[[4r9a]], [[Resolution|resolution]] 1.20&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LAT:BETA-LACTOSE'>LAT</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4r9b|4r9b]], [[4r9c|4r9c]], [[4r9d|4r9d]], [[4rl7|4rl7]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4r9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r9a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4r9a RCSB], [http://www.ebi.ac.uk/pdbsum/4r9a PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4r9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r9a OCA], [http://pdbe.org/4r9a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r9a RCSB], [http://www.ebi.ac.uk/pdbsum/4r9a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r9a ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4r9a" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Galectin|Galectin]]
 == References ==
 <references/>

4r9a

From Proteopedia

Revision as of 17:17, 18 January 2017

Crystal structure of Human galectin-3 CRD in complex with lactose (pH 7.0, PEG4000)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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