2ech

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(Difference between revisions)

Revision as of 08:19, 25 December 2014

ECHISTATIN-THE REFINED STRUCTURE OF A DISINTEGRIN IN SOLUTION BY 1H NMR

Structural highlights

2ech 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.
NonStd Res:
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[DISI_ECHCA] 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

The structure of the disintegrin echistatin has been determined by 1H NMR, distance geometry calculations and restrained molecular dynamics simulations. The structure has been refined from the preliminary distance geometry calculations with the inclusion of additional 1H NMR data and hydrogen bonds identified in early stages of the molecular dynamics calculations. The calculations reported here allow a distinction to be made between the two possible disulfide bridging patterns-echistatin is crosslinked as follows: Cys2-Cys11, Cys7-Cys32, Cys8-Cys37, Cys20-Cys39. The final set of structures gives an average pairwise root mean square distance of 0.100 nm (calculated over the backbone atoms of residues Ser4-Cys20 and Asp30-Pro40). The core of echistatin is a well defined though irregular structure, composed of a series of non-classical turns crosslinked by the disulfide bridges and stabilised by hydrogen bonds. The RGD sequence is located in a protruding loop whose stem is formed by two rigid, hydrogen-bonded strands (Thr18-Cys20, Asp30-Cys32). The RGD sequence is connected to this structure by short, flexible segments. High (but not unlimited) mobility is probably necessary for fast recognition and fitting to the integrin receptors. Sequence variability among the disintegrins is found in the segments flanking the RGD sequence, suggesting that these may be important in conferring specificity for the receptors.

Echistatin: the refined structure of a disintegrin in solution by 1H NMR and restrained molecular dynamics.,Atkinson RA, Saudek V, Pelton JT Int J Pept Protein Res. 1994 Jun;43(6):563-72. PMID:7928087^[4]

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

References

↑ 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
↑ 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
↑ 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
↑ Atkinson RA, Saudek V, Pelton JT. Echistatin: the refined structure of a disintegrin in solution by 1H NMR and restrained molecular dynamics. Int J Pept Protein Res. 1994 Jun;43(6):563-72. PMID:7928087

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/2ech"

Categories: Echis carinatus | Atkinson, R A | Pelton, J T | Saudek, V | Blood coagulation inhibitor

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2ech]] 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=2ECH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ECH FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
+</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></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=2ech FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ech OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ech RCSB], [http://www.ebi.ac.uk/pdbsum/2ech PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ech FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ech OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ech RCSB], [http://www.ebi.ac.uk/pdbsum/2ech PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/DISI_ECHCA DISI_ECHCA]] 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:3198653</ref> <ref>PMID:2320569</ref> <ref>PMID:9269775</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 32: / Line 34: @@
 </StructureSection>
 [[Category: Echis carinatus]]
-[[Category: Atkinson, R A.]]
+[[Category: Atkinson, R A]]
-[[Category: Pelton, J T.]]
+[[Category: Pelton, J T]]
-[[Category: Saudek, V.]]
+[[Category: Saudek, V]]
 [[Category: Blood coagulation inhibitor]]

2ech

From Proteopedia

Revision as of 08:19, 25 December 2014

ECHISTATIN-THE REFINED STRUCTURE OF A DISINTEGRIN IN SOLUTION BY 1H NMR

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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