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| | ==Crystal structure of agkisacucetin, a GpIb-binding snaclec (snake C-type lectin) that inhibits platelet== | | ==Crystal structure of agkisacucetin, a GpIb-binding snaclec (snake C-type lectin) that inhibits platelet== |
| - | <StructureSection load='3ubu' size='340' side='right' caption='[[3ubu]], [[Resolution|resolution]] 1.91Å' scene=''> | + | <StructureSection load='3ubu' size='340' side='right'caption='[[3ubu]], [[Resolution|resolution]] 1.91Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ubu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Deinagkistrodon_acutus Deinagkistrodon acutus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UBU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UBU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ubu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Deinagkistrodon_acutus Deinagkistrodon acutus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UBU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UBU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.91Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=3ubu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ubu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ubu RCSB], [http://www.ebi.ac.uk/pdbsum/3ubu PDBsum]</span></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=3ubu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ubu OCA], [https://pdbe.org/3ubu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ubu RCSB], [https://www.ebi.ac.uk/pdbsum/3ubu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ubu ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AGGA1_DEIAC AGGA1_DEIAC]] Agglucetin specifically causes platelet aggregation and surface exposure of integrin alpha-IIb/beta-3 with a GPIb-(GP1BA-) dependent manner in washed platelets. It binds to human platelets in a saturable manner, and its binding is specifically blocked by anti-GP Ib mAb. It regulates endothelial cell survival and promotes angiogenesis by activating integrin alpha-v/beta-3 signaling through FAK/phosphatidylinositol 3-kinase (PI3K)/Akt pathway.<ref>PMID:11686327</ref> <ref>PMID:18312855</ref> [[http://www.uniprot.org/uniprot/AGGB2_DEIAC AGGB2_DEIAC]] Agglucetin specifically causes platelet aggregation and surface exposure of integrin alpha-IIb/beta-3 with a GPIb-(GP1BA-) dependent manner in washed platelets. It binds to human platelets in a saturable manner, and its binding is specifically blocked by anti-GP Ib mAb. It regulates endothelial cell survival and promotes angiogenesis by activating integrin alpha-v/beta-3 signaling through FAK/phosphatidylinositol 3-kinase (PI3K)/Akt pathway.<ref>PMID:11686327</ref> <ref>PMID:18312855</ref> | + | [https://www.uniprot.org/uniprot/SLA1_DEIAC SLA1_DEIAC] Agglucetin specifically causes platelet aggregation and surface exposure of integrin alpha-IIb/beta-3 with a GPIb-(GP1BA-) dependent manner in washed platelets. It binds to human platelets in a saturable manner, and its binding is specifically blocked by anti-GP Ib mAb. It regulates endothelial cell survival and promotes angiogenesis by activating integrin alpha-v/beta-3 signaling through FAK/phosphatidylinositol 3-kinase (PI3K)/Akt pathway.<ref>PMID:11686327</ref> <ref>PMID:18312855</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 3ubu" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Deinagkistrodon acutus]] | | [[Category: Deinagkistrodon acutus]] |
| - | [[Category: Chen, H]] | + | [[Category: Large Structures]] |
| - | [[Category: Gao, Y]] | + | [[Category: Chen H]] |
| - | [[Category: Ge, H]] | + | [[Category: Gao Y]] |
| - | [[Category: Li, H]] | + | [[Category: Ge H]] |
| - | [[Category: Liu, Y]] | + | [[Category: Li H]] |
| - | [[Category: Niu, L]] | + | [[Category: Liu Y]] |
| - | [[Category: Teng, M]] | + | [[Category: Niu L]] |
| - | [[Category: Agkisacucetin]]
| + | [[Category: Teng M]] |
| - | [[Category: C-type lectin-like]]
| + | |
| - | [[Category: Dimer]]
| + | |
| - | [[Category: Gpib binding]]
| + | |
| - | [[Category: Gpib inhibitor]]
| + | |
| - | [[Category: Platelet inhibiting]]
| + | |
| - | [[Category: Toxin]]
| + | |
| Structural highlights
Function
SLA1_DEIAC Agglucetin specifically causes platelet aggregation and surface exposure of integrin alpha-IIb/beta-3 with a GPIb-(GP1BA-) dependent manner in washed platelets. It binds to human platelets in a saturable manner, and its binding is specifically blocked by anti-GP Ib mAb. It regulates endothelial cell survival and promotes angiogenesis by activating integrin alpha-v/beta-3 signaling through FAK/phosphatidylinositol 3-kinase (PI3K)/Akt pathway.[1] [2]
Publication Abstract from PubMed
Agkisacucetin is a snake C-type lectin isolated from the venom of Agkistrodon acutus (A. acutus). It binds specifically to the platelet glycoprotein (GP) Ib and prevents the von Willebrand factor (VWF) accessing it. We determined the crystal structure of agkisacucetin to 1.9A resolution. The structure of agkisacucetin has an (alphabeta) fold similar to another GPIb-binding protein, flavocetin-A, but lacks the C-terminal cysteine in the beta-subunit, does not form (betaalpha)(4) tetramers, and does not cluster GPIbs, like flavocetin-A.
Crystal structure of agkisacucetin, a Gpib-binding snake C-type lectin that inhibits platelet adhesion and aggregation.,Gao Y, Ge H, Chen H, Li H, Liu Y, Chen L, Li X, Liu J, Niu L, Teng M Proteins. 2012 Jun;80(6):1707-11. doi: 10.1002/prot.24060. Epub 2012 Mar 23. PMID:22447656[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang WJ, Huang TF. A novel tetrameric venom protein, agglucetin from Agkistrodon acutus, acts as a glycoprotein Ib agonist. Thromb Haemost. 2001 Oct;86(4):1077-86. PMID:11686327
- ↑ Wang WJ. Agglucetin, a tetrameric C-type lectin-like venom protein, regulates endothelial cell survival and promotes angiogenesis by activating integrin alphavbeta3 signaling. Biochem Biophys Res Commun. 2008 May 2;369(2):753-60. doi:, 10.1016/j.bbrc.2008.02.091. Epub 2008 Feb 27. PMID:18312855 doi:http://dx.doi.org/10.1016/j.bbrc.2008.02.091
- ↑ Gao Y, Ge H, Chen H, Li H, Liu Y, Chen L, Li X, Liu J, Niu L, Teng M. Crystal structure of agkisacucetin, a Gpib-binding snake C-type lectin that inhibits platelet adhesion and aggregation. Proteins. 2012 Feb 22. doi: 10.1002/prot.24060. PMID:22447656 doi:10.1002/prot.24060
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