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| | ==Crystal structure of Agrocybe aegerita lectin AAL mutant F93G== | | ==Crystal structure of Agrocybe aegerita lectin AAL mutant F93G== |
| - | <StructureSection load='2zgt' size='340' side='right' caption='[[2zgt]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='2zgt' size='340' side='right'caption='[[2zgt]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2zgt]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Agrae Agrae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZGT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZGT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2zgt]] is a 2 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=2ZGT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZGT FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2zgk|2zgk]], [[2zgl|2zgl]], [[2zgm|2zgm]], [[2zgn|2zgn]], [[2zgo|2zgo]], [[2zgp|2zgp]], [[2zgq|2zgq]], [[2zgr|2zgr]], [[2zgs|2zgs]], [[2zgu|2zgu]]</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]] 2.8Å</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 AGRAE])</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=2zgt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zgt OCA], [https://pdbe.org/2zgt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zgt RCSB], [https://www.ebi.ac.uk/pdbsum/2zgt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zgt 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=2zgt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zgt OCA], [http://pdbe.org/2zgt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zgt RCSB], [http://www.ebi.ac.uk/pdbsum/2zgt 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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zg/2zgt_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zg/2zgt_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Agrae]] | + | [[Category: Cyclocybe aegerita]] |
| - | [[Category: Li, D F]] | + | [[Category: Large Structures]] |
| - | [[Category: Wang, D C]] | + | [[Category: Li DF]] |
| - | [[Category: Yang, N]] | + | [[Category: Wang DC]] |
| - | [[Category: Apoptosis]] | + | [[Category: Yang N]] |
| - | [[Category: Galectin]]
| + | |
| - | [[Category: Hydrolase]]
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| - | [[Category: Jelly roll]]
| + | |
| - | [[Category: Nuclease]]
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| 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]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Lectin AAL (Agrocybe aegerita lectin) from the edible mushroom A. aegerita is an antitumor protein that exerts its tumor-suppressing function via apoptosis-inducing activity in cancer cells. The crystal structures of ligand-free AAL and its complex with lactose have been determined. The AAL structure shows a dimeric organization, and each protomer adopts a prototype galectin fold. To identify the structural determinants for antitumor effects arising from the apoptosis-inducing activity of AAL, 11 mutants were prepared and subjected to comprehensive investigations covering oligomerization detection, carbohydrate binding test, apoptosis-inducing activity assay, and X-ray crystallographic analysis. The results show that dimerization of AAL is a prerequisite for its tumor cell apoptosis-inducing activity, and both galactose and glucose are basic moieties of functional carbohydrate ligands for lectin bioactivity. Furthermore, we have identified a hydrophobic pocket that is essential for the protein's apoptosis-inducing activity but independent of its carbohydrate binding and dimer formation. This hydrophobic pocket comprises a hydrophobic cluster including residues Leu33, Leu35, Phe93, and Ile144, and is involved in AAL's function mechanism as an integrated structural motif. Single mutants such as F93G or I144G do not disrupt carbohydrate binding and homodimerization capabilities, but abolish the bioactivity of the protein. These findings reveal the structural basis for the antitumor property of AAL, which may lead to de novo designs of antitumor drugs based on AAL as a prototype model.
Structural basis for the tumor cell apoptosis-inducing activity of an antitumor lectin from the edible mushroom Agrocybe aegerita.,Yang N, Li DF, Feng L, Xiang Y, Liu W, Sun H, Wang DC J Mol Biol. 2009 Apr 3;387(3):694-705. Epub 2009 Feb 9. PMID:19361423[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
- ↑ Yang N, Li DF, Feng L, Xiang Y, Liu W, Sun H, Wang DC. Structural basis for the tumor cell apoptosis-inducing activity of an antitumor lectin from the edible mushroom Agrocybe aegerita. J Mol Biol. 2009 Apr 3;387(3):694-705. Epub 2009 Feb 9. PMID:19361423 doi:10.1016/j.jmb.2009.02.002
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