This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

1ro3

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 06:31, 2 March 2022

New structural insights on short disintegrin echistatin by NMR

Structural highlights

1ro3 is a 1 chain structure with sequence from Echis carinatus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2ech
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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:15535803^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Dennis MS, Henzel WJ, Pitti RM, Lipari MT, Napier MA, Deisher TA, Bunting S, Lazarus RA. Platelet glycoprotein IIb-IIIa protein antagonists from snake venoms: evidence for a family of platelet-aggregation inhibitors. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2471-5. PMID:2320569
↑ Gan ZR, Gould RJ, Jacobs JW, Friedman PA, Polokoff MA. Echistatin. A potent platelet aggregation inhibitor from the venom of the viper, Echis carinatus. J Biol Chem. 1988 Dec 25;263(36):19827-32. PMID:3198653
↑ Marcinkiewicz C, Vijay-Kumar S, McLane MA, Niewiarowski S. Significance of RGD loop and C-terminal domain of echistatin for recognition of alphaIIb beta3 and alpha(v) beta3 integrins and expression of ligand-induced binding site. Blood. 1997 Aug 15;90(4):1565-75. PMID:9269775
↑ Monleon D, Esteve V, Kovacs H, Calvete JJ, Celda B. Conformation and concerted dynamics of the integrin-binding site and the C-terminal region of echistatin revealed by homonuclear NMR. Biochem J. 2005 Apr 1;387(Pt 1):57-66. PMID:15535803 doi:http://dx.doi.org/10.1042/BJ20041343

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1ro3"

@@ Line 3: / Line 3: @@
 <StructureSection load='1ro3' size='340' side='right'caption='[[1ro3]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1ro3]] is a 1 chain structure with sequence from [http://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 [http://proteopedia.org/fgij/fg.htm?mol=1RO3 FirstGlance]. <br>
+<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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ech|2ech]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2ech|2ech]]</div></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1ro3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ro3 OCA], [http://pdbe.org/1ro3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ro3 RCSB], [http://www.ebi.ac.uk/pdbsum/1ro3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ro3 ProSAT]</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=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 ==
-[[http://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>
+[[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]]

1ro3

From Proteopedia

Revision as of 06:31, 2 March 2022

New structural insights on short disintegrin echistatin by NMR

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox