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6lsq
From Proteopedia
(Difference between revisions)
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==Crystal structure of Echistatin, an RGD-containing short disintegrin== | ==Crystal structure of Echistatin, an RGD-containing short disintegrin== | ||
| - | <StructureSection load='6lsq' size='340' side='right'caption='[[6lsq]]' scene=''> | + | <StructureSection load='6lsq' size='340' side='right'caption='[[6lsq]], [[Resolution|resolution]] 1.80Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LSQ OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6lsq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Echis_carinatus Echis carinatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LSQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LSQ FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[https://proteopedia.org/fgij/fg.htm?mol=6lsq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lsq OCA], [https://pdbe.org/6lsq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lsq RCSB], [https://www.ebi.ac.uk/pdbsum/6lsq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lsq ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/VM2EA_ECHCS VM2EA_ECHCS] Potent inhibitor of ligand binding to the integrins alpha-V/beta-3 (ITGAV/ITGB3), alpha-5/beta-1 (ITGA5/ITGB1) and alpha-IIb/beta-3 (ITGA2B/ITGB3). Competition with fibrinogen for the RGD recognition sites on the alpha-IIb/beta-3 integrin (glyco-protein IIb/IIIa complex) results in the inhibition of platelet aggregation and other antithrombotic properties such as an ability to prevent coronary thrombosis in animal models. Is also a potent inhibitor of bone resorption. This results from the blocking of the interaction of alpha-V/beta-3 integrin on the surface of osteoclasts with bone extracellular matrix. In addition, interaction with alpha-V/beta-3 also inhibits adhesion of human umbilical vein endothelial cells (HUVEC) to immobilized vitronectin and fibronectin.<ref>PMID:2320569</ref> <ref>PMID:3198653</ref> <ref>PMID:9269775</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Echistatin (Ech) is a short disintegrin with a long (42)NPHKGPAT C-terminal tail. We determined the 3-D structure of Ech by X-ray crystallography. Superimposition of the structures of chains A and B showed conformational differences in their RGD loops and C-termini. The chain A structure is consistent with our NMR analysis that the GPAT residues of the C-terminus cannot be observed due to high flexibility. The hydrogen bond patterns of the RGD loop and between the RGD loop and C-terminus in Ech were the same as those of the corresponding residues in medium disintegrins. The mutant with C-terminal HKGPAT truncation caused 6.4-, 7.0-, 11.7-, and 18.6-fold decreases in inhibiting integrins alphavbeta3, alphaIIbbeta3, alphavbeta5, and alpha5beta1. Mutagenesis of the C-terminus showed that the H44A mutant caused 2.5- and 4.4-fold increases in inhibiting alphaIIbbeta3 and alpha5beta1, and the K45A mutant caused a 2.6-fold decrease in inhibiting alphaIIbbeta3. We found that Ech inhibited VEGF-induced HUVEC proliferation with an IC50 value of 103.2 nM and inhibited the migration of A375, U373MG, and Panc-1 tumor cells with IC50 values of 1.5, 5.7, and 154.5 nM. These findings suggest that Ech is a potential anticancer agent, and its C-terminal region can be optimized to improve its anticancer activity. | ||
| + | |||
| + | Structural Insight into Integrin Recognition and Anticancer Activity of Echistatin.,Chen YC, Chang YT, Chen CY, Shiu JH, Cheng CH, Huang CH, Chen JF, Chuang WJ Toxins (Basel). 2020 Nov 9;12(11). pii: toxins12110709. doi:, 10.3390/toxins12110709. PMID:33182321<ref>PMID:33182321</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6lsq" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Disintegrin|Disintegrin]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Echis carinatus]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Chang YT]] | [[Category: Chang YT]] | ||
[[Category: Chen YC]] | [[Category: Chen YC]] | ||
[[Category: Chuang WJ]] | [[Category: Chuang WJ]] | ||
Current revision
Crystal structure of Echistatin, an RGD-containing short disintegrin
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