1ro3: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1ro3.gif|left|200px]]<br /><applet load="1ro3" size="350" 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://oca.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://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:52:54 2008''