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PDBsum entry 2pjf

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protein links
Hydrolase PDB id
2pjf
Jmol
Contents
Protein chain
68 a.a. *
* Residue conservation analysis
PDB id:
2pjf
Name: Hydrolase
Title: Solution structure of rhodostomin
Structure: Rhodostoxin-disintegrin rhodostomin. Chain: a. Fragment: residues 1-68. Engineered: yes
Source: Calloselasma rhodostoma. Malayan pit viper. Organism_taxid: 8717. Gene: rhod. Expressed in: pichia pastoris. Expression_system_taxid: 4922.
NMR struc: 20 models
Authors: W.J.Chuang,Y.C.Chen,C.Y.Chen,Y.T.Chang
Key ref:
C.Y.Chen et al. (2009). Effect of D to E mutation of the RGD motif in rhodostomin on its activity, structure, and dynamics: importance of the interactions between the D residue and integrin. Proteins, 76, 808-821. PubMed id: 19280603 DOI: 10.1002/prot.22387
Date:
16-Apr-07     Release date:   08-May-07    
Supersedes: 1jyp
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P30403  (VM2RH_CALRH) -  Zinc metalloproteinase/disintegrin
Seq:
Struc:
478 a.a.
68 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1002/prot.22387 Proteins 76:808-821 (2009)
PubMed id: 19280603  
 
 
Effect of D to E mutation of the RGD motif in rhodostomin on its activity, structure, and dynamics: importance of the interactions between the D residue and integrin.
C.Y.Chen, J.H.Shiu, Y.H.Hsieh, Y.C.Liu, Y.C.Chen, Y.C.Chen, W.Y.Jeng, M.J.Tang, S.J.Lo, W.J.Chuang.
 
  ABSTRACT  
 
Rhodostomin (Rho) is a snake venom protein containing an RGD motif that specifically inhibits the integrin-binding function. Rho produced in Pichia pastoris inhibits platelet aggregation with a K(I) of 78 nM as potent as native Rho. In contrast, its D51E mutant inhibits platelet aggregation with a K(I) of 49 muM. Structural analysis of Rho and its D51E mutant showed that they have the same tertiary fold with three two-stranded antiparallel beta-sheets. There are no structural backbone differences between the RG[D/E] loop which extends outward from the protein core and the RG[D/E] sequence at its apex in a four-residue RG[D/E]M type I turn. Two minor differences between Rho and its D51E mutant were only found from their backbone dynamics and 3D structures. The R(2) value of E51 is 13% higher than that of the D51 residue. A difference in the charge separation of 1.76 A was found between the sidechains of positive (R49) and negative residues (D51 or E51).The docking of Rho into integrin alphavbeta3 showed that the backbone amide and carbonyl groups of the D51 residue of Rho were formed hydrogen bonds with the integrin residues R216 and R214, respectively. In contrast, these hydrogen bonds were absent in the D51E mutant-integrin complex. Our findings suggest that the interactions between both the sidechain and backbone of the D residue of RGD-containing ligands and integrin are important for their binding.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Structure of Rho and its D51E Mutant. Stereoview of 20 lowest-energy NMR structures of Rho (A) and its D51E mutant (B). Ribbon representation of the averaged structure of Rho (C). The -strands, disulfide bonds, and the sidechains in the RGD motif of Rho are shown in light blue, red, and blue, respectively.
Figure 3.
Figure 3. Superimpositions of the 3D structures of Rho (2PJF) and trimestatin (1J2L) (A), and Rho and kistrin (1N4Y) (B). Rho, trimestatin, and kistrin are shown in red, grey, and green, respectively.
 
  The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2009, 76, 808-821) copyright 2009.  
  Figures were selected by an automated process.