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| | ==Crystal Structure of Agrocybe aegerita lectin AAL mutant E66A complexed with p-Nitrophenyl Thomsen-Friedenreich disaccharide== | | ==Crystal Structure of Agrocybe aegerita lectin AAL mutant E66A complexed with p-Nitrophenyl Thomsen-Friedenreich disaccharide== |
| - | <StructureSection load='3m3e' size='340' side='right' caption='[[3m3e]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='3m3e' size='340' side='right'caption='[[3m3e]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3m3e]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Agrocybe_aegerita Agrocybe aegerita]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3M3E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3M3E FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3m3e]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Cyclocybe_aegerita Cyclocybe aegerita]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3M3E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3M3E FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NPO:P-NITROPHENOL'>NPO</scene>, <scene name='pdbligand=A2G:N-ACETYL-2-DEOXY-2-AMINO-GALACTOSE'>A2G</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3afk|3afk]], [[3m3c|3m3c]], [[3m3o|3m3o]], [[3m3q|3m3q]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A2G:N-ACETYL-2-DEOXY-2-AMINO-GALACTOSE'>A2G</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=NPO:P-NITROPHENOL'>NPO</scene>, <scene name='pdbligand=PRD_900084:Thomsen-Friedenreich+antigen'>PRD_900084</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AAL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5400 Agrocybe aegerita])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3m3e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3m3e OCA], [https://pdbe.org/3m3e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3m3e RCSB], [https://www.ebi.ac.uk/pdbsum/3m3e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3m3e ProSAT]</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=3m3e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3m3e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3m3e RCSB], [http://www.ebi.ac.uk/pdbsum/3m3e PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ATLE_AGRAE ATLE_AGRAE]] Anti-tumor lectin with DNase activity. Inhibits the growth of several tumor cell lines in vitro. Induces lymphocyte infiltration and necrosis of tumor cells in a mouse tumor model. Induces apoptosis in HeLa cells.<ref>PMID:12757412</ref> | + | [https://www.uniprot.org/uniprot/ATLE_CYCAE ATLE_CYCAE] Anti-tumor lectin with DNase activity. Inhibits the growth of several tumor cell lines in vitro. Induces lymphocyte infiltration and necrosis of tumor cells in a mouse tumor model. Induces apoptosis in HeLa cells. Binds N-acetylneuraminyl lactose (N-acetyl-alpha-neuraminyl-(2->3)-beta-D-galactosyl-(1->4)-beta-D-glucose) (PubMed:16051274).<ref>PMID:12757412</ref> <ref>PMID:16051274</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3m3e" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Agrocybe aegerita]] | + | [[Category: Cyclocybe aegerita]] |
| - | [[Category: Feng, L]] | + | [[Category: Large Structures]] |
| - | [[Category: Li, D]] | + | [[Category: Feng L]] |
| - | [[Category: Wang, D]] | + | [[Category: Li D]] |
| - | [[Category: 3-galnac-alpha-o-p-nitrophenyl]] | + | [[Category: Wang D]] |
| - | [[Category: Aal]]
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| - | [[Category: Apoptosis]]
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| - | [[Category: Gal-beta-1]]
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| - | [[Category: Galectin]]
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| - | [[Category: Hydrolase]]
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| - | [[Category: Lectin]]
| + | |
| - | [[Category: Mutant]]
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| - | [[Category: Nuclease]]
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| - | [[Category: Thomsen-friedenreich disaccharide]]
| + | |
| Structural highlights
Function
ATLE_CYCAE Anti-tumor lectin with DNase activity. Inhibits the growth of several tumor cell lines in vitro. Induces lymphocyte infiltration and necrosis of tumor cells in a mouse tumor model. Induces apoptosis in HeLa cells. Binds N-acetylneuraminyl lactose (N-acetyl-alpha-neuraminyl-(2->3)-beta-D-galactosyl-(1->4)-beta-D-glucose) (PubMed:16051274).[1] [2]
Publication Abstract from PubMed
Thomsen-Friedenreich (TF) antigen, which plays an important role in the regulation of cancer cell proliferation, occurs in approximately 90% of all human cancers and precancerous conditions. Although TF antigen has been known for almost 80 yr as a pancarcinoma antigen, the recognition mechanism between TF antigen and target protein has not been structurally characterized. A number of studies indicated that TF disaccharide is a potential ligand of the galactoside-binding galectins. In this work, we identified the TF antigen as a potential ligand of the antitumor galectin AAL (Agrocybe aegerita lectin) through glycan array analysis and reported the crystal structure of AAL complexed with the TF antigen. The structure provides a first look at the recognition mode between AAL and TF antigen, which is unique in a conservative (Glu-water-Arg-water) structural motif-based hydrogen bond network. Structure-based mutagenesis analysis further revealed the residues responsible for recognition specificity and binding affinity. Crystal structures of AAL complexed with two other TF-containing glycans showed that the unique TF recognition mode is kept intact, which may be commonly adopted in some cancer-related galectins. The finding provided the new target and approach for the antitumor drug design and relative strategy based on the AAL-TF recognition mode as a prototype model.
Structural insights into the recognition mechanism between an antitumor galectin AAL and the Thomsen-Friedenreich antigen.,Feng L, Sun H, Zhang Y, Li DF, Wang DC FASEB J. 2010 Oct;24(10):3861-8. Epub 2010 Jun 7. PMID:20530247[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zhao C, Sun H, Tong X, Qi Y. An antitumour lectin from the edible mushroom Agrocybe aegerita. Biochem J. 2003 Sep 1;374(Pt 2):321-7. PMID:12757412 doi:10.1042/BJ20030300
- ↑ Ban M, Yoon HJ, Demirkan E, Utsumi S, Mikami B, Yagi F. Structural basis of a fungal galectin from Agrocybe cylindracea for recognizing sialoconjugate. J Mol Biol. 2005 Aug 26;351(4):695-706. PMID:16051274 doi:10.1016/j.jmb.2005.06.045
- ↑ Feng L, Sun H, Zhang Y, Li DF, Wang DC. Structural insights into the recognition mechanism between an antitumor galectin AAL and the Thomsen-Friedenreich antigen. FASEB J. 2010 Oct;24(10):3861-8. Epub 2010 Jun 7. PMID:20530247 doi:10.1096/fj.10-159111
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