1ro3: Difference between revisions
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'''New structural insights on short disintegrin echistatin by NMR''' | '''New structural insights on short disintegrin echistatin by NMR''' | ||
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[[Category: Marcinkiewicz, C.]] | [[Category: Marcinkiewicz, C.]] | ||
[[Category: Monleon, D.]] | [[Category: Monleon, D.]] | ||
[[Category: | [[Category: No regular secondary structure]] | ||
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Revision as of 07:43, 3 May 2008
New structural insights on short disintegrin echistatin by NMR
OverviewOverview
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.
About this StructureAbout this Structure
1RO3 is a Single protein structure of sequence from Echis carinatus. Full crystallographic information is available from OCA.
ReferenceReference
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 Page seeded by OCA on Sat May 3 07:43:06 2008