PDBsum entry 1ro3

Go to PDB code: 
protein links
Cell adhesion PDB id
Protein chain
49 a.a. *
* Residue conservation analysis
PDB id:
Name: Cell adhesion
Title: New structural insights on short disintegrin echistatin by nmr
Structure: Disintegrin echistatin. Chain: a. Synonym: platelet aggregation activation inhibitor, carinatin
Source: Echis carinatus. Saw-scaled viper. Organism_taxid: 40353
NMR struc: 20 models
Authors: D.Monleon,V.Esteve,J.J.Calvete,C.Marcinkiewicz,B.Celda
Key ref: D.Monleón et al. (2005). Conformation and concerted dynamics of the integrin-binding site and the C-terminal region of echistatin revealed by homonuclear NMR. Biochem J, 387, 57-66. PubMed id: 15535803 DOI: 10.1042/BJ20041343
01-Dec-03     Release date:   09-Dec-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P17347  (DISEA_ECHCS) -  Disintegrin echistatin-alpha
49 a.a.
49 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 


DOI no: 10.1042/BJ20041343 Biochem J 387:57-66 (2005)
PubMed id: 15535803  
Conformation and concerted dynamics of the integrin-binding site and the C-terminal region of echistatin revealed by homonuclear NMR.
D.Monleón, V.Esteve, H.Kovacs, J.J.Calvete, B.Celda.
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.

Literature references that cite this PDB file's key reference

  PubMed id Reference
18391413 N.Moiseeva, R.Bau, S.D.Swenson, F.S.Markland, J.Y.Choe, Z.J.Liu, and M.Allaire (2008).
Structure of acostatin, a dimeric disintegrin from Southern copperhead (Agkistrodon contortrix contortrix), at 1.7 A resolution.
  Acta Crystallogr D Biol Crystallogr, 64, 466-470.
PDB code: 3c05
17612732 G.Grégoire, M.P.Gaigeot, D.C.Marinica, J.Lemaire, J.P.Schermann, and C.Desfrançois (2007).
Resonant infrared multiphoton dissociation spectroscopy of gas-phase protonated peptides. Experiments and Car-Parrinello dynamics at 300 K.
  Phys Chem Chem Phys, 9, 3082-3097.  
16877710 R.R.Hantgan, M.C.Stahle, J.H.Connor, D.A.Horita, M.Rocco, M.A.McLane, S.Yakovlev, and L.Medved (2006).
Integrin alphaIIbbeta3:ligand interactions are linked to binding-site remodeling.
  Protein Sci, 15, 1893-1906.  
16737347 S.C.Wagstaff, G.D.Laing, R.D.Theakston, C.Papaspyridis, and R.A.Harrison (2006).
Bioinformatics and multiepitope DNA immunization to design rational snake antivenom.
  PLoS Med, 3, e184.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.