PDBsum entry 1ro3

Cell adhesion

PDB id: 1ro3

Contents

Protein chain

49 a.a. *

* Residue conservation analysis

PDB id:

1ro3

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

Date:

01-Dec-03 Release date: 09-Dec-03

Protein chain

P17347  (VM2EA_ECHCS) -  Disintegrin metalloproteinase/disintegrin echistatin (Fragment) from Echis carinatus sochureki

Seq: 186 a.a.

Struc: 49 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.4.24.- - ?????

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.

ABSTRACT

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.