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| | ==Expression in Pichia pastoris and backbone dynamics of dendroaspin, a three finger toxin== | | ==Expression in Pichia pastoris and backbone dynamics of dendroaspin, a three finger toxin== |
| - | <StructureSection load='2la1' size='340' side='right' caption='[[2la1]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2la1' size='340' side='right'caption='[[2la1]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2la1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Dendroaspis_jamesoni_kaimosae Dendroaspis jamesoni kaimosae]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LA1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LA1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2la1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Dendroaspis_jamesoni_kaimosae Dendroaspis jamesoni kaimosae]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LA1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LA1 FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2la1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2la1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2la1 RCSB], [http://www.ebi.ac.uk/pdbsum/2la1 PDBsum]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr> |
| - | <table> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2la1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2la1 OCA], [https://pdbe.org/2la1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2la1 RCSB], [https://www.ebi.ac.uk/pdbsum/2la1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2la1 ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/3SPM_DENJA 3SPM_DENJA] Inhibits ADP-induced platelet aggregation and inhibits the binding of purified platelet fibrinogen receptor alpha-IIb/beta-3 (ITGA2B/ITGB3) to immobilized fibrinogen (PubMed:1591238). Has also been described to inhibit cell adhesion to fibrinogen, fibronectin, laminin and collagen (PubMed:11336631, PubMed:16798616).<ref>PMID:11336631</ref> <ref>PMID:1591238</ref> <ref>PMID:16798616</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 2la1" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Dendroaspis jamesoni kaimosae]] | | [[Category: Dendroaspis jamesoni kaimosae]] |
| - | [[Category: Chen, Y C.]] | + | [[Category: Large Structures]] |
| - | [[Category: Cheng, C H.]] | + | [[Category: Chen YC]] |
| - | [[Category: Chuang, W J.]] | + | [[Category: Cheng CH]] |
| - | [[Category: Shiu, J H.]] | + | [[Category: Chuang WJ]] |
| - | [[Category: Dendroaspin]] | + | [[Category: Shiu JH]] |
| - | [[Category: Disintegrin]]
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| - | [[Category: Integrin]]
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| - | [[Category: Snake toxin]]
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| - | [[Category: Three-finger fold]]
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| - | [[Category: Toxin]]
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| Structural highlights
Function
3SPM_DENJA Inhibits ADP-induced platelet aggregation and inhibits the binding of purified platelet fibrinogen receptor alpha-IIb/beta-3 (ITGA2B/ITGB3) to immobilized fibrinogen (PubMed:1591238). Has also been described to inhibit cell adhesion to fibrinogen, fibronectin, laminin and collagen (PubMed:11336631, PubMed:16798616).[1] [2] [3]
Publication Abstract from PubMed
Dendroaspin (Den) and rhodostomin (Rho) are snake venom proteins containing a PRGDMP motif. Although Den and Rho have different 3D structures, they are highly potent integrin inhibitors. To study their structure, function, and dynamics relationships, we expressed Den and Rho in Pichia pastoris. The recombinant Den and Rho inhibited platelet aggregation with the K(I) values of 149.8 and 83.2 nM. Cell adhesion analysis showed that Den was 3.7 times less active than Rho when inhibiting the integrin alphaIIbbeta3 and 2.5 times less active when inhibiting the integrin alphavbeta3. In contrast, Den and Rho were similarly active when inhibiting the integrin alpha5beta1 with the IC(50) values of 239.8 and 256.8 nM. NMR analysis showed that recombinant Den and Rho have different 3D conformations for their arginyl-glycyl-aspartic acid (RGD) motif. However, the comparison with Rho showed that the docking of Den into integrin alphavbeta3 resulted in a similar number of contacts. Analysis of the dynamic properties of the RGD loop in Den and Rho showed that they also had different dynamic properties. These results demonstrate that protein scaffolds affect the function, structure, and dynamics of their RGD motif.
Dynamics and functional differences between dendroaspin and rhodostomin: Insights into protein scaffolds in integrin recognition.,Cheng CH, Chen YC, Shiu JH, Chang YT, Chang YS, Huang CH, Chen CY, Chuang WJ Protein Sci. 2012 Dec;21(12):1872-84. doi: 10.1002/pro.2169. Epub 2012 Nov 6. PMID:23033223[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wattam B, Shang D, Rahman S, Egglezou S, Scully M, Kakkar V, Lu X. Arg-Tyr-Asp (RYD) and Arg-Cys-Asp (RCD) motifs in dendroaspin promote selective inhibition of beta1 and beta3 integrins. Biochem J. 2001 May 15;356(Pt 1):11-7. PMID:11336631 doi:10.1042/0264-6021:3560011
- ↑ McDowell RS, Dennis MS, Louie A, Shuster M, Mulkerrin MG, Lazarus RA. Mambin, a potent glycoprotein IIb-IIIa antagonist and platelet aggregation inhibitor structurally related to the short neurotoxins. Biochemistry. 1992 May 26;31(20):4766-72. PMID:1591238 doi:10.1021/bi00135a004
- ↑ Lu X, Davies J, Lu D, Xia M, Wattam B, Shang D, Sun Y, Scully M, Kakkar V. The effect of the single substitution of arginine within the RGD tripeptide motif of a modified neurotoxin dendroaspin on its activity of platelet aggregation and cell adhesion. Cell Commun Adhes. 2006 May-Jun;13(3):171-83. PMID:16798616 doi:10.1080/15419060600726183
- ↑ Cheng CH, Chen YC, Shiu JH, Chang YT, Chang YS, Huang CH, Chen CY, Chuang WJ. Dynamics and functional differences between dendroaspin and rhodostomin: Insights into protein scaffolds in integrin recognition. Protein Sci. 2012 Dec;21(12):1872-84. doi: 10.1002/pro.2169. Epub 2012 Nov 6. PMID:23033223 doi:http://dx.doi.org/10.1002/pro.2169
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