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PDBsum entry 1j2l

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Toxin PDB id
1j2l
Jmol
Contents
Protein chain
68 a.a. *
Ligands
SO4
Waters ×153
* Residue conservation analysis
PDB id:
1j2l
Name: Toxin
Title: Crystal structure of the disintegrin, trimestatin
Structure: Disintegrin triflavin. Chain: a. Synonym: trimestatin, rgd-containing peptide
Source: Trimeresurus flavoviridis. Organism_taxid: 88087. Secretion: venom
Resolution:
1.70Å     R-factor:   0.187     R-free:   0.238
Authors: Y.Fujii,D.Okuda,Z.Fujimoto,T.Morita,H.Mizuno
Key ref:
Y.Fujii et al. (2003). Crystal structure of trimestatin, a disintegrin containing a cell adhesion recognition motif RGD. J Mol Biol, 332, 1115-1122. PubMed id: 14499613 DOI: 10.1016/S0022-2836(03)00991-4
Date:
06-Jan-03     Release date:   07-Oct-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P21859  (DIST_PROFL) -  Disintegrin triflavin
Seq:
Struc:
70 a.a.
68 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

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

 

 
DOI no: 10.1016/S0022-2836(03)00991-4 J Mol Biol 332:1115-1122 (2003)
PubMed id: 14499613  
 
 
Crystal structure of trimestatin, a disintegrin containing a cell adhesion recognition motif RGD.
Y.Fujii, D.Okuda, Z.Fujimoto, K.Horii, T.Morita, H.Mizuno.
 
  ABSTRACT  
 
Disintegrins are a family of small proteins containing an Arg-Gly-Asp (RGD) sequence motif that binds specifically to integrin receptors. Since the integrin is known to serve as the final common pathway leading to aggregation via formation of platelet-platelet bridges, disintegrins act as fibrinogen receptor antagonists. Here, we report the first crystal structure of a disintegrin, trimestatin, found in snake venom. The structure of trimestatin at 1.7A resolution reveals that a number of turns and loops form a rigid core stabilized by six disulfide bonds. Electron densities of the RGD sequence are visible clearly at the tip of a hairpin loop, in such a manner that the Arg and Asp side-chains point in opposite directions. A docking model using the crystal structure of integrin alphaVbeta3 suggests that the Arg binds to the propeller domain, and Asp to the betaA domain. This model indicates that the C-terminal region is another potential binding site with integrin receptors. In addition to the RGD sequence, the structural evidence of a C-terminal region (Arg66, Trp67 and Asn68) important for disintegrin activity allows understanding of the high affinity and selectiveness of snake venom disintegrin for integrin receptors. The crystal structure of trimestatin should provide a useful framework for designing and developing more effective drugs for controlling platelet aggregation and anti-angiogenesis cancer.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Stereo view of trimestatin. (a) A backbone ribbon trace with the two C-terminal residues omitted. The RGD sequence, amino acid residues adjacent to the RGD sequence and the C-terminal residues (considered important for receptor-binding) are labeled and their side-chains are indicated in ball-and-stick presentation. The six disulfide bonds are depicted in ball-and-stick presentation. The Figure was generated using MOLSCRIPT[37.] and Raster3D. [38.] (b) The 2F[o] -F[c] electron density map at 1.7 Å resolution, contoured at 1.5s around the RGD sequence. Portions of symmetry-related neighboring molecules that interact with side-chains of the RGD sequence are indicated in different colors. The Figure was generated using QUANTA 2000 (Accerlys, USA).
Figure 3.
Figure 3. A putative trimestatin-receptor interaction. (a) Representation of trimestatin (green) docked on the surface of aVb3 (PDB code 1L5G; orange, the propeller domain of aV subunit; yellow, the bA domain of b3 subunit; blue spheres, manganese ions at MIDAS and ADMIDAS sites[18.]). The side-chains of the RGD sequence are labeled and indicated in ball-and-stick presentation. The corresponding RGD sequence of the cyclic peptide ligand in 1L5G is superimposed in gray ball-and-stick presentation for comparison. The side-chains of the C-terminal residues that interact with receptors are also labeled and indicated in ball-and-stick presentation. The Figure was generated using WebLabViewerLite /-. (b) A close-up stereo view of the interaction region. Residues involving interactions are shown in ball-and-stick presentation with labels. Oxygen and nitrogen atoms are in red and blue, respectively. Interactions except hydrophobic contacts are shown by dotted lines. The Figure was generated using MOLSCRIPT[37.] and Raster3D. [38.]
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 332, 1115-1122) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21334359 S.Lucena, E.E.Sanchez, and J.C.Perez (2011).
Anti-metastatic activity of the recombinant disintegrin, r-mojastin 1, from the Mohave rattlesnake.
  Toxicon, 57, 794-802.  
20532165 R.O.Minea, C.M.Helchowski, S.J.Zidovetzki, F.K.Costa, S.D.Swenson, and F.S.Markland (2010).
Vicrostatin - an anti-invasive multi-integrin targeting chimeric disintegrin with tumor anti-angiogenic and pro-apoptotic activities.
  PLoS One, 5, e10929.  
18706512 S.Takeda (2009).
Three-dimensional domain architecture of the ADAM family proteinases.
  Semin Cell Dev Biol, 20, 146-152.  
18042673 L.Mosyak, K.Georgiadis, T.Shane, K.Svenson, T.Hebert, T.McDonagh, S.Mackie, S.Olland, L.Lin, X.Zhong, R.Kriz, E.L.Reifenberg, L.A.Collins-Racie, C.Corcoran, B.Freeman, R.Zollner, T.Marvell, M.Vera, P.E.Sum, E.R.Lavallie, M.Stahl, and W.Somers (2008).
Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5.
  Protein Sci, 17, 16-21.
PDB codes: 2rjp 2rjq 3b2z
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
17952617 O.H.Ramos, A.Kauskot, M.R.Cominetti, I.Bechyne, C.L.Salla Pontes, F.Chareyre, J.Manent, R.Vassy, M.Giovannini, C.Legrand, H.S.Selistre-de-Araujo, M.Crépin, and A.Bonnefoy (2008).
A novel alpha(v)beta (3)-blocking disintegrin containing the RGD motive, DisBa-01, inhibits bFGF-induced angiogenesis and melanoma metastasis.
  Clin Exp Metastasis, 25, 53-64.  
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.  
16688218 S.Takeda, T.Igarashi, H.Mori, and S.Araki (2006).
Crystal structures of VAP1 reveal ADAMs' MDC domain architecture and its unique C-shaped scaffold.
  EMBO J, 25, 2388-2396.
PDB codes: 2ero 2erp 2erq
17146059 W.Gao, P.J.Anderson, E.M.Majerus, E.A.Tuley, and J.E.Sadler (2006).
Exosite interactions contribute to tension-induced cleavage of von Willebrand factor by the antithrombotic ADAMTS13 metalloprotease.
  Proc Natl Acad Sci U S A, 103, 19099-19104.  
16239734 E.Jakobsson, J.Nilsson, D.Ogg, and G.J.Kleywegt (2005).
Structure of human semicarbazide-sensitive amine oxidase/vascular adhesion protein-1.
  Acta Crystallogr D Biol Crystallogr, 61, 1550-1562.
PDB codes: 2c10 2c11
16102046 Q.Lu, J.M.Clemetson, and K.J.Clemetson (2005).
Snake venoms and hemostasis.
  J Thromb Haemost, 3, 1791-1799.  
15388950 Y.L.Wang, K.X.Goh, W.G.Wu, and C.J.Chen (2004).
Purification, crystallization and preliminary X-ray crystallographic analysis of a cysteine-rich secretory protein (CRISP) from Naja atra venom.
  Acta Crystallogr D Biol Crystallogr, 60, 1912-1915.  
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 codes are shown on the right.