1ro3: Difference between revisions

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-[[Image:1ro3.gif|left|200px]]<br /><applet load="1ro3" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1ro3" />
-'''New structural insights on short disintegrin echistatin by NMR'''<br />
-==Overview==
+==New structural insights on short disintegrin echistatin by NMR==
-Echistatin is a potent antagonist of the integrins alpha(v)beta3, alpha5beta1 and alpha(IIb)beta3. Its full inhibitory activity depends on, an RGD (Arg-Gly-Asp) motif expressed at the tip of the integrin-binding, loop and on its C-terminal tail. Previous NMR structures of echistatin, showed a poorly defined integrin-recognition sequence and an incomplete, C-terminal tail, which left the molecular basis of the functional synergy, between the RGD loop and the C-terminal region unresolved. We report a, high-resolution structure of echistatin and an analysis of its internal, motions by off-resonance ROESY (rotating-frame Overhauser enhancement, spectroscopy). The full-length C-terminal polypeptide is visible as a, beta-hairpin running parallel to the RGD loop and exposing at the tip, residues Pro43, His44 and Lys45. The side chains of the amino acids of the, RGD motif have well-defined conformations. The integrin-binding loop, displays an overall movement with maximal amplitude of 30 degrees ., Internal angular motions in the 100-300 ps timescale indicate increased, flexibility for the backbone atoms at the base of the integrin-recognition, loop. In addition, backbone atoms of the amino acids Ala23 (flanking the, R24GD26 tripeptide) and Asp26 of the integrin-binding motif showed, increased angular mobility, suggesting the existence of major and minor, hinge effects at the base and the tip, respectively, of the RGD loop. A, strong network of NOEs (nuclear Overhauser effects) between residues of, the RGD loop and the C-terminal tail indicate concerted motions between, these two functional regions. A full-length echistatin-alpha(v)beta3, docking model suggests that echistatin's C-terminal amino acids may, contact alpha(v)-subunit residues and provides new insights to delineate, structure-function correlations.
+<StructureSection load='1ro3' size='340' side='right'caption='[[1ro3]]' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1ro3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Echis_carinatus Echis carinatus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RO3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RO3 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1ro3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ro3 OCA], [https://pdbe.org/1ro3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ro3 RCSB], [https://www.ebi.ac.uk/pdbsum/1ro3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ro3 ProSAT]</span></td></tr>
+</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>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ro/1ro3_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ro3 ConSurf].
+<div style="clear:both"></div>
-==About this Structure==
+==See Also==
-RO3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Echis_carinatus Echis carinatus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1RO3 OCA].
+*[[Disintegrin|Disintegrin]]
+== References ==
-==Reference==
+<references/>
-Conformation and concerted dynamics of the integrin-binding site and the C-terminal region of echistatin revealed by homonuclear NMR., Monleon D, Esteve V, Kovacs H, Calvete JJ, Celda B, Biochem J. 2005 Apr 1;387(Pt 1):57-66. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15535803 15535803]
+__TOC__
+</StructureSection>
 [[Category: Echis carinatus]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Calvete, J.J.]]
+[[Category: Calvete JJ]]
-[[Category: Celda, B.]]
+[[Category: Celda B]]
-[[Category: Esteve, V.]]
+[[Category: Esteve V]]
-[[Category: Marcinkiewicz, C.]]
+[[Category: Marcinkiewicz C]]
-[[Category: Monleon, D.]]
+[[Category: Monleon D]]
-[[Category: no regular secondary structure]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 01:44:46 2007''