PDBsum entry 1fvl

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Blood coagulation inhibitor PDB id
Protein chain
70 a.a. *
* Residue conservation analysis
PDB id:
Name: Blood coagulation inhibitor
Title: The nuclear magnetic resonance solution structure of flavoridin, an antagonist of the platelet gp iib-iiia receptor
Structure: Flavoridin. Chain: a
Source: Trimeresurus flavoviridis. Organism_taxid: 88087. Organ: blood
NMR struc: 18 models
Authors: H.Senn,W.Klaus
Key ref: H.Senn and W.Klaus (1993). The nuclear magnetic resonance solution structure of flavoridin, an antagonist of the platelet GP IIb-IIIa receptor. J Mol Biol, 232, 907-925. PubMed id: 8355277
06-Sep-95     Release date:   29-Jan-96    
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Protein chain
Pfam   ArchSchema ?
P18619  (VM2FL_PROFL) -  Zinc metalloproteinase/disintegrin
483 a.a.
70 a.a.
Key:    PfamA domain  Secondary structure  CATH domain


J Mol Biol 232:907-925 (1993)
PubMed id: 8355277  
The nuclear magnetic resonance solution structure of flavoridin, an antagonist of the platelet GP IIb-IIIa receptor.
H.Senn, W.Klaus.
The snake venom protein flavoridin, a polypeptide of 70 amino acid residues, is a potent inhibitor of blood platelet aggregation. It binds to cell-surface integrin receptors such as the fibrinogen receptor glycoprotein IIb/IIIa. The inhibitory properties of flavoridin have been attributed to the tripeptide segment Arg-Gly-Asp (residues 49 to 51). This paper describes the determination of the three-dimensional structure of flavoridin in aqueous solution based on two-dimensional nuclear magnetic resonance spectroscopy. A family of 18 conformers was selected to characterize the solution structure. The molecule comprises two structural domains, an N-terminal unit extending from residues 1 to 25, and a C-terminal unit from residues 26 to 70. Whereas the mutual spatial orientation of these regions is not well defined, each one is well organized within itself. The segment 26 to 70, which is homologous to the sequence of the snake toxins echistatin and eristostatin, shows an average value of 1.0 A for the root-mean-square deviations of the backbone atoms among the 18 conformers. The structure of flavoridin consists essentially of non-repetitive elements such as tight turns and loops, whose location and conformation are characterized in this paper. With the exception of two short regions of antiparallel beta-sheet, no classic element of protein secondary structure is present. The six disulphide bridges, which have been mapped by applying a novel computational strategy (see accompanying paper), are the dominant organizational feature of the polypeptide fold of flavoridin. Two of the bridges are located in the N-terminal domain, three in the C-terminal domain and one connects the two structural units. The mobile RGD recognition sequence for integrins is located peripheral to the core region of the C-terminal domain at the most exposed end of a nine residue loop structure, which is attached to a short beta-sheet. The C terminus is close to this loop structure.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20526749 C.Auriemma, M.Viscardi, S.Tafuri, L.M.Pavone, F.Capuano, L.Rinaldi, R.Della Morte, G.Iovane, and N.Staiano (2010).
Integrin receptors play a role in the internalin B-dependent entry of Listeria monocytogenes into host cells.
  Cell Mol Biol Lett, 15, 496-506.  
18479462 J.W.Fox, and S.M.Serrano (2008).
Insights into and speculations about snake venom metalloproteinase (SVMP) synthesis, folding and disulfide bond formation and their contribution to venom complexity.
  FEBS J, 275, 3016-3030.  
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.  
15927747 A.Scibelli, G.Matteoli, S.Roperto, E.Alimenti, L.Dipineto, L.M.Pavone, R.Della Morte, L.F.Menna, A.Fioretti, and N.Staiano (2005).
Flavoridin inhibits Yersinia enterocolitica uptake into fibronectin-adherent HeLa cells.
  FEMS Microbiol Lett, 247, 51-57.  
16279943 I.Simões, E.C.Mueller, A.Otto, D.Bur, A.Y.Cheung, C.Faro, and E.Pires (2005).
Molecular analysis of the interaction between cardosin A and phospholipase D(alpha). Identification of RGD/KGE sequences as binding motifs for C2 domains.
  FEBS J, 272, 5786-5798.  
15390258 J.H.Shiu, C.Y.Chen, L.S.Chang, Y.C.Chen, Y.C.Chen, Y.H.Lo, Y.C.Liu, and W.J.Chuang (2004).
Solution structure of gamma-bungarotoxin: the functional significance of amino acid residues flanking the RGD motif in integrin binding.
  Proteins, 57, 839-849.
PDB code: 1mr6
12947085 D.Monleon, M.P.Moreno-Murciano, H.Kovacs, C.Marcinkiewicz, J.J.Calvete, and B.Celda (2003).
Concerted motions of the integrin-binding loop and the C-terminal tail of the non-RGD disintegrin obtustatin.
  J Biol Chem, 278, 45570-45576.  
12538900 M.P.Moreno-Murciano, D.Monleón, J.J.Calvete, B.Celda, and C.Marcinkiewicz (2003).
Amino acid sequence and homology modeling of obtustatin, a novel non-RGD-containing short disintegrin isolated from the venom of Vipera lebetina obtusa.
  Protein Sci, 12, 366-371.  
11932256 B.J.Mans, A.I.Louw, and A.W.Neitz (2002).
Savignygrin, a platelet aggregation inhibitor from the soft tick Ornithodoros savignyi, presents the RGD integrin recognition motif on the Kunitz-BPTI fold.
  J Biol Chem, 277, 21371-21378.  
11877740 H.S.Park, C.Kim, and Y.K.Kang (2002).
Preferred conformations of RGDX tetrapeptides to inhibit the binding of fibrinogen to platelets.
  Biopolymers, 63, 298-313.  
  11771727 M.R.Ritter, Q.Zhou, and F.S.Markland (2001).
Contortrostatin, a homodimeric disintegrin, actively disrupts focal adhesion and cytoskeletal structure and inhibits cell motility through a novel mechanism.
  Cell Commun Adhes, 8, 71-86.  
11340665 R.T.Guo, L.J.Chou, Y.C.Chen, C.Y.Chen, K.Pari, C.J.Jen, S.J.Lo, S.L.Huang, C.Y.Lee, T.W.Chang, and W.J.Chaung (2001).
Expression in Pichia pastoris and characterization by circular dichroism and NMR of rhodostomin.
  Proteins, 43, 499-508.  
  10975565 A.M.Krezel, J.S.Ulmer, G.Wagner, and R.A.Lazarus (2000).
Recombinant decorsin: dynamics of the RGD recognition site.
  Protein Sci, 9, 1428-1438.  
10212222 C.Marcinkiewicz, J.J.Calvete, M.M.Marcinkiewicz, M.Raida, S.Vijay-Kumar, Z.Huang, R.R.Lobb, and S.Niewiarowski (1999).
EC3, a novel heterodimeric disintegrin from Echis carinatus venom, inhibits alpha4 and alpha5 integrins in an RGD-independent manner.
  J Biol Chem, 274, 12468-12473.  
10608843 I.Wierzbicka-Patynowski, S.Niewiarowski, C.Marcinkiewicz, J.J.Calvete, M.M.Marcinkiewicz, and M.A.McLane (1999).
Structural requirements of echistatin for the recognition of alpha(v)beta(3) and alpha(5)beta(1) integrins.
  J Biol Chem, 274, 37809-37814.  
9920897 J.Ivaska, J.Käpylä, O.Pentikäinen, A.M.Hoffrén, J.Hermonen, P.Huttunen, M.S.Johnson, and J.Heino (1999).
A peptide inhibiting the collagen binding function of integrin alpha2I domain.
  J Biol Chem, 274, 3513-3521.  
8970741 E.Ruoslahti (1996).
RGD and other recognition sequences for integrins.
  Annu Rev Cell Dev Biol, 12, 697-715.  
7568238 A.Kidera (1995).
Enhanced conformational sampling in Monte Carlo simulations of proteins: application to a constrained peptide.
  Proc Natl Acad Sci U S A, 92, 9886-9889.  
7836460 R.Kodandapani, B.Veerapandian, T.J.Kunicki, and K.R.Ely (1995).
Crystal structure of the OPG2 Fab. An antireceptor antibody that mimics an RGD cell adhesion site.
  J Biol Chem, 270, 2268-2273.
PDB code: 1opg
7634091 M.J.Sutcliffe, M.Jaseja, E.I.Hyde, X.Lu, and J.A.Williams (1994).
Three-dimensional structure of the RGD-containing neurotoxin homologue dendroaspin.
  Nat Struct Biol, 1, 802-807.
PDB code: 1drs
7813476 M.Jaseja, X.Lu, J.A.Williams, M.J.Sutcliffe, V.V.Kakkar, R.A.Parslow, and E.I.Hyde (1994).
1H-NMR assignments and secondary structure of dendroaspin, an RGD-containing glycoprotein IIb-IIIa (alpha IIb-beta 3) antagonist with a neurotoxin fold.
  Eur J Biochem, 226, 861-868.  
8281937 M.Jaseja, K.J.Smith, X.Lu, J.A.Williams, H.Trayer, I.P.Trayer, and E.I.Hyde (1993).
1H-NMR studies and secondary structure of the RGD-containing snake toxin, albolabrin.
  Eur J Biochem, 218, 853-860.  
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.