spacer
spacer

PDBsum entry 1toc
Go to PDB code: 
protein Protein-protein interface(s) links
Complex (hydrolase/inhibitor) PDB id
1toc

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chains
28 a.a. *
259 a.a. *
120 a.a. *
Waters ×31
* Residue conservation analysis
PDB id:
1toc
Name: Complex (hydrolase/inhibitor)
Title: Structure of serine proteinase
Structure: Thrombin. Chain: a, c, e, g. Engineered: yes. Thrombin. Chain: b, d, f, h. Engineered: yes. Ornithodorin. Chain: r, s, t, u. Engineered: yes
Source: Bos taurus. Cattle. Organism_taxid: 9913. Tissue: plasma. Expressed in: escherichia coli. Expression_system_taxid: 562. Ornithodoros moubata. Organism_taxid: 6938.
Biol. unit: Not given
Resolution:
3.10Å     R-factor:   0.230    
Authors: A.Van De Locht,R.Huber,W.Bode
Key ref: A.van de Locht et al. (1996). The ornithodorin-thrombin crystal structure, a key to the TAP enigma? Embo J, 15, 6011-6017. PubMed id: 8947023
Date:
20-Jul-96     Release date:   23-Jul-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00735  (THRB_BOVIN) -  Prothrombin from Bos taurus
Seq:
Struc: 		 
Seq:
Struc: 		625 a.a.
28 a.a.
Protein chains
Pfam   ArchSchema ?
P00735  (THRB_BOVIN) -  Prothrombin from Bos taurus
Seq:
Struc: 		 
Seq:
Struc: 		625 a.a.
259 a.a.
Protein chains
Pfam   ArchSchema ?
P56409  (KUNI_ORNMO) -  Ornithodorin from Ornithodoros moubata
Seq:
Struc: 		119 a.a.
120 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D, E, F, G, H: E.C.3.4.21.5  - thrombin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage: Arg-|-Gly; activates fibrinogen to fibrin and releases fibrinopeptide A and B.

 

 
Embo J 15:6011-6017 (1996)
PubMed id: 8947023  
 
 
The ornithodorin-thrombin crystal structure, a key to the TAP enigma?
A.van de Locht, M.T.Stubbs, W.Bode, T.Friedrich, C.Bollschweiler, W.Höffken, R.Huber.
 
  ABSTRACT  
 
Ornithodorin, isolated from the blood sucking soft tick Ornithodoros moubata, is a potent (Ki = 10(-12) M) and highly selective thrombin inhibitor. Internal sequence homology indicates a two domain protein. Each domain resembles the Kunitz inhibitor basic pancreatic trypsin inhibitor (BPTI) and also the tick anticoagulant peptide (TAP) isolated from the same organism. The 3.1 A crystal structure of the ornithodorin-thrombin complex confirms that both domains of ornithodorin exhibit a distorted BPTI-like fold. The N-terminal portion and the C-terminal helix of each domain are structurally very similar to BPTI, whereas the regions corresponding to the binding loop of BPTI adopt different conformations. Neither of the two 'reactive site loops' of ornithodorin contacts the protease in the ornithodorin-thrombin complex. Instead, the N-terminal residues of ornithodorin bind to the active site of thrombin, reminiscent of the thrombin-hirudin interaction. The C-terminal domain binds at the fibrinogen recognition exosite. Molecular recognition of its target protease by this double-headed Kunitz-type inhibitor diverges considerably from other members of this intensely studied superfamily. The complex structure provides a model to explain the perplexing results of mutagenesis studies on the TAP-factor Xa interaction.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21423674 Anisuzzaman, M.K.Islam, M.A.Alim, T.Miyoshi, T.Hatta, K.Yamaji, Y.Matsumoto, K.Fujisaki, and N.Tsuji (2011).
Longistatin, a plasminogen activator, is key to the availability of blood-meals for ixodid ticks.
  PLoS Pathog, 7, e1001312.  
19273185 I.M.Francischetti, A.Sa-Nunes, B.J.Mans, I.M.Santos, and J.M.Ribeiro (2009).
The role of saliva in tick feeding.
  Front Biosci, 14, 2051-2088.  
18070664 B.J.Mans, J.F.Andersen, I.M.Francischetti, J.G.Valenzuela, T.G.Schwan, V.M.Pham, M.K.Garfield, C.H.Hammer, and J.M.Ribeiro (2008).
Comparative sialomics between hard and soft ticks: implications for the evolution of blood-feeding behavior.
  Insect Biochem Mol Biol, 38, 42-58.  
21082917 C.Y.Koh, and R.M.Kini (2008).
Anticoagulants from hematophagous animals.
  Expert Rev Hematol, 1, 135-139.  
18070662 I.M.Francischetti, B.J.Mans, Z.Meng, N.Gudderra, T.D.Veenstra, V.M.Pham, and J.M.Ribeiro (2008).
An insight into the sialome of the soft tick, Ornithodorus parkeri.
  Insect Biochem Mol Biol, 38, 1.  
19021911 J.M.Anderson, D.E.Sonenshine, and J.G.Valenzuela (2008).
Exploring the mialome of ticks: An annotated catalogue of midgut transcripts from the hard tick, Dermacentor variabilis (Acari: Ixodidae).
  BMC Genomics, 9, 552.  
18271624 J.W.Hovius, M.Levi, and E.Fikrig (2008).
Salivating for knowledge: potential pharmacological agents in tick saliva.
  PLoS Med, 5, e43.  
18286181 S.Macedo-Ribeiro, C.Almeida, B.M.Calisto, T.Friedrich, R.Mentele, J.Stürzebecher, P.Fuentes-Prior, and P.J.Pereira (2008).
Isolation, cloning and structural characterisation of boophilin, a multifunctional Kunitz-type proteinase inhibitor from the cattle tick.
  PLoS ONE, 3, e1624.
PDB code: 2ody
17684009 C.Y.Koh, M.Kazimirova, A.Trimnell, P.Takac, M.Labuda, P.A.Nuttall, and R.M.Kini (2007).
Variegin, a novel fast and tight binding thrombin inhibitor from the tropical bont tick.
  J Biol Chem, 282, 29101-29113.  
17164520 J.Janin, F.Rodier, P.Chakrabarti, and R.P.Bahadur (2007).
Macromolecular recognition in the Protein Data Bank.
  Acta Crystallogr D Biol Crystallogr, 63, 1-8.  
17575982 R.N.Araujo, I.T.Campos, A.S.Tanaka, A.Santos, N.F.Gontijo, M.J.Lehane, and M.H.Pereira (2007).
Brasiliensin: A novel intestinal thrombin inhibitor from Triatoma brasiliensis (Hemiptera: Reduviidae) with an important role in blood intake.
  Int J Parasitol, 37, 1351-1358.  
16757887 C.Nakajima, S.Imamura, S.Konnai, S.Yamada, H.Nishikado, K.Ohashi, and M.Onuma (2006).
A novel gene encoding a thrombin inhibitory protein in a cDNA library from Haemaphysalis longicornis salivary gland.
  J Vet Med Sci, 68, 447-452.  
15775973 J.Otlewski, F.Jelen, M.Zakrzewska, and A.Oleksy (2005).
The many faces of protease-protein inhibitor interaction.
  EMBO J, 24, 1303-1310.  
15892855 W.Bode (2005).
The structure of thrombin, a chameleon-like proteinase.
  J Thromb Haemost, 3, 2379-2388.  
15259776 L.Kovár (2004).
Tick saliva in anti-tick immunity and pathogen transmission.
  Folia Microbiol (Praha), 49, 327-336.  
14607082 J.A.Huntington, and T.P.Baglin (2003).
Targeting thrombin--rational drug design from natural mechanisms.
  Trends Pharmacol Sci, 24, 589-595.  
12112698 F.R.Melo, D.J.Rigden, O.L.Franco, L.V.Mello, M.B.Ary, M.F.Grossi de Sá, and C.Bloch (2002).
Inhibition of trypsin by cowpea thionin: characterization, molecular modeling, and docking.
  Proteins, 48, 311-319.  
11948787 P.Chakrabarti, and J.Janin (2002).
Dissecting protein-protein recognition sites.
  Proteins, 47, 334-343.  
11060016 J.L.Richardson, B.Kröger, W.Hoeffken, J.E.Sadler, P.Pereira, R.Huber, W.Bode, and P.Fuentes-Prior (2000).
Crystal structure of the human alpha-thrombin-haemadin complex: an exosite II-binding inhibitor.
  EMBO J, 19, 5650-5660.
PDB code: 1e0f
  10716178 R.St Charles, K.Padmanabhan, R.V.Arni, K.P.Padmanabhan, and A.Tulinsky (2000).
Structure of tick anticoagulant peptide at 1.6 A resolution complexed with bovine pancreatic trypsin inhibitor.
  Protein Sci, 9, 265-272.
PDB code: 1d0d
  10210187 A.Lombardi, G.De Simone, F.Nastri, S.Galdiero, R.Della Morte, N.Staiano, C.Pedone, M.Bolognesi, and V.Pavone (1999).
The crystal structure of alpha-thrombin-hirunorm IV complex reveals a novel specificity site recognition mode.
  Protein Sci, 8, 91-95.
PDB code: 4thn
10380350 A.Lombardi, G.De Simone, S.Galdiero, N.Staiano, F.Nastri, and V.Pavone (1999).
From natural to synthetic multisite thrombin inhibitors.
  Biopolymers, 51, 19-39.  
10561601 K.Mende, O.Petoukhova, V.Koulitchkova, G.A.Schaub, U.Lange, R.Kaufmann, and G.Nowak (1999).
Dipetalogastin, a potent thrombin inhibitor from the blood-sucking insect. Dipetalogaster maximus cDNA cloning, expression and characterization.
  Eur J Biochem, 266, 583-590.  
10091588 R.De Cristofaro, and R.Landolfi (1999).
Allosteric modulation of BPTI interaction with human alpha- and zeta-thrombin.
  Eur J Biochem, 260, 97.  
  9521099 G.De Simone, A.Lombardi, S.Galdiero, F.Nastri, R.Della Morte, N.Staiano, C.Pedone, M.Bolognesi, and V.Pavone (1998).
Hirunorms are true hirudin mimetics. The crystal structure of human alpha-thrombin-hirunorm V complex.
  Protein Sci, 7, 243-253.
PDB code: 5gds
9214615 A.van de Locht, W.Bode, R.Huber, B.F.Le Bonniec, S.R.Stone, C.T.Esmon, and M.T.Stubbs (1997).
The thrombin E192Q-BPTI complex reveals gross structural rearrangements: implications for the interaction with antithrombin and thrombomodulin.
  EMBO J, 16, 2977-2984.
PDB code: 1bth
9336216 J.Klingler, and T.Friedrich (1997).
Site-specific interaction of thrombin and inhibitors observed by fluorescence correlation spectroscopy.
  Biophys J, 73, 2195-2200.  
9342325 P.Fuentes-Prior, C.Noeske-Jungblut, P.Donner, W.D.Schleuning, R.Huber, and W.Bode (1997).
Structure of the thrombin complex with triabin, a lipocalin-like exosite-binding inhibitor derived from a triatomine bug.
  Proc Natl Acad Sci U S A, 94, 11845-11850.
PDB code: 1avg
9346315 V.Arocas, H.C.Castro, R.B.Zingali, M.C.Guillin, M.Jandrot-Perrus, C.Bon, and A.Wisner (1997).
Molecular cloning and expression of bothrojaracin, a potent thrombin inhibitor from snake venom.
  Eur J Biochem, 248, 550-557.  
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.

 

spacer
spacer