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PDBsum entry 1tbr
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protein Protein-protein interface(s) links
Complex (serine protease/inhibitor) PDB id
1tbr

 

 

 

 

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Contents
Protein chains
49 a.a. *
259 a.a. *
103 a.a. *
Waters ×203
* Residue conservation analysis
PDB id:
1tbr
Name: Complex (serine protease/inhibitor)
Title: Crystal structure of insect derived double domain kazal inhibitor rhodniin in complex with thrombin
Structure: Thrombin. Chain: l, j. Thrombin. Chain: h, k. Rhodniin. Chain: r, s. Engineered: yes
Source: Bos taurus. Cattle. Organism_taxid: 9913. Organ: plasma. Rhodnius prolixus. Organism_taxid: 13249. Gene: prpti. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Hexamer (from PQS)
Resolution:
2.60Å     R-factor:   0.189     R-free:   0.263
Authors: A.Van De Locht,D.Lamba,W.Bode
Key ref: A.van de Locht et al. (1995). Two heads are better than one: crystal structure of the insect derived double domain Kazal inhibitor rhodniin in complex with thrombin. Embo J, 14, 5149-5157. PubMed id: 7489704
Date:
03-Mar-95     Release date:   14-Oct-96    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00735  (THRB_BOVIN) -  Prothrombin from Bos taurus
Seq:
Struc: 		 
Seq:
Struc: 		625 a.a.
49 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 ?
Q06684  (THBI_RHOPR) -  Thrombin inhibitor rhodniin from Rhodnius prolixus
Seq:
Struc: 		103 a.a.
103 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains L, H, J, K: 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 14:5149-5157 (1995)
PubMed id: 7489704  
 
 
Two heads are better than one: crystal structure of the insect derived double domain Kazal inhibitor rhodniin in complex with thrombin.
A.van de Locht, D.Lamba, M.Bauer, R.Huber, T.Friedrich, B.Kröger, W.Höffken, W.Bode.
 
  ABSTRACT  
 
Rhodniin is a highly specific inhibitor of thrombin isolated from the assassin bug Rhodnius prolixus. The 2.6 Angstrum crystal structure of the non-covalent complex between recombinant rhodniin and bovine alpha-thrombin reveals that the two Kazal-type domains of rhodniin bind to different sites of thrombin. The amino-terminal domain binds in a substrate-like manner to the narrow active-site cleft of thrombin; the imidazole group of the P1 His residue extends into the S1 pocket to form favourable hydrogen/ionic bonds with Asp189 at its bottom, and additionally with Glu192 at its entrance. The carboxy-terminal domain, whose distorted reactive-site loop cannot adopt the canonical conformation, docks to the fibrinogen recognition exosite via extensive electrostatic interactions. The rather acidic polypeptide linking the two domains is displaced from the thrombin surface, with none of its residues involved in direct salt bridges with thrombin. The tight (Ki = 2 x 10(-13) M) binding of rhodniin to thrombin is the result of the sum of steric and charge complementarity of the amino-terminal domain towards the active-site cleft, and of the electrostatic interactions between the carboxy-terminal domain and the exosite.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20015075 E.Calvo, F.Tokumasu, D.M.Mizurini, P.McPhie, D.L.Narum, J.M.Ribeiro, R.Q.Monteiro, and I.M.Francischetti (2010).
Aegyptin displays high-affinity for the von Willebrand factor binding site (RGQOGVMGF) in collagen and inhibits carotid thrombus formation in vivo.
  FEBS J, 277, 413-427.  
21158638 G.S.Min, I.N.Sarkar, and M.E.Siddall (2010).
Salivary transcriptome of the North American medicinal leech, Macrobdella decora.
  J Parasitol, 96, 1211-1221.  
19845005 A.A.McFarlane, and J.Stetefeld (2009).
An interdomain disulfide bridge links the NtA and first FS domain in agrin.
  Protein Sci, 18, 2421-2428.
PDB code: 3i70
21082917 C.Y.Koh, and R.M.Kini (2008).
Anticoagulants from hematophagous animals.
  Expert Rev Hematol, 1, 135-139.  
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
18207082 T.C.Assumpção, I.M.Francischetti, J.F.Andersen, A.Schwarz, J.M.Santana, and J.M.Ribeiro (2008).
An insight into the sialome of the blood-sucking bug Triatoma infestans, a vector of Chagas' disease.
  Insect Biochem Mol Biol, 38, 213-232.  
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.  
16374478 A.Tartaglia-Polcini, C.Bonnart, A.Micheloni, F.Cianfarani, A.Andrè, G.Zambruno, A.Hovnanian, and M.D'Alessio (2006).
SPINK5, the defective gene in netherton syndrome, encodes multiple LEKTI isoforms derived from alternative pre-mRNA processing.
  J Invest Dermatol, 126, 315-324.  
15756478 B.Jarasrassamee, P.Supungul, S.Panyim, S.Klinbunga, V.Rimphanichayakit, and A.Tassanakajon (2005).
Recombinant expression and characterization of five-domain Kazal-type serine proteinase inhibitor of black tiger shrimp (Penaeus monodon).
  Mar Biotechnol (NY), 7, 46-52.  
15892855 W.Bode (2005).
The structure of thrombin, a chameleon-like proteinase.
  J Thromb Haemost, 3, 2379-2388.  
15502324 I.T.Campos, B.G.Guimarães, F.J.Medrano, A.S.Tanaka, and J.A.Barbosa (2004).
Crystallization, data collection and phasing of infestin 4, a factor XIIa inhibitor.
  Acta Crystallogr D Biol Crystallogr, 60, 2051-2053.  
15162489 S.Liu, C.Zhang, H.Zhou, and Y.Zhou (2004).
A physical reference state unifies the structure-derived potential of mean force for protein folding and binding.
  Proteins, 56, 93.  
12867435 C.A.Innis, and M.Hyvönen (2003).
Crystal structures of the heparan sulfate-binding domain of follistatin. Insights into ligand binding.
  J Biol Chem, 278, 39969-39977.
PDB codes: 1lr7 1lr8 1lr9
14607082 J.A.Huntington, and T.P.Baglin (2003).
Targeting thrombin--rational drug design from natural mechanisms.
  Trends Pharmacol Sci, 24, 589-595.  
12186551 H.Hemmi, T.Yoshida, T.Kumazaki, N.Nemoto, J.Hasegawa, F.Nishioka, Y.Kyogoku, H.Yokosawa, and Y.Kobayashi (2002).
Solution structure of ascidian trypsin inhibitor determined by nuclear magnetic resonance spectroscopy.
  Biochemistry, 41, 10657-10664.
PDB code: 1iw4
12228242 M.T.Morris, A.Coppin, S.Tomavo, and V.B.Carruthers (2002).
Functional analysis of Toxoplasma gondii protease inhibitor 1.
  J Biol Chem, 277, 45259-45266.  
11121104 T.Myles, B.F.Le Bonniec, and S.R.Stone (2001).
The dual role of thrombin's anion-binding exosite-I in the recognition and cleavage of the protease-activated receptor 1.
  Eur J Biochem, 268, 70-77.  
11277929 X.Nirmala, D.Kodrík, M.Zurovec, and F.Sehnal (2001).
Insect silk contains both a Kunitz-type and a unique Kazal-type proteinase inhibitor.
  Eur J Biochem, 268, 2064-2073.  
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
  15535586 M.S.Cupp, D.Zhang, and E.W.Cupp (2000).
Horn fly (Diptera: Muscidae) saliva targets thrombin action in hemostasis.
  J Med Entomol, 37, 416-421.  
11058753 W.R.Montfort, A.Weichsel, and J.F.Andersen (2000).
Nitrophorins and related antihemostatic lipocalins from Rhodnius prolixus and other blood-sucking arthropods.
  Biochim Biophys Acta, 1482, 110-118.  
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.  
10102985 H.Czapinska, and J.Otlewski (1999).
Structural and energetic determinants of the S1-site specificity in serine proteases.
  Eur J Biochem, 260, 571-595.  
10387040 H.Jhoti, A.Cleasby, S.Reid, P.J.Thomas, M.Weir, and A.Wonacott (1999).
Crystal structures of thrombin complexed to a novel series of synthetic inhibitors containing a 5,5-trans-lactone template.
  Biochemistry, 38, 7969-7977.
PDB codes: 1qhr 1qj1 1qj6 1qj7
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.  
10542076 T.Niimi, H.Yokoyama, A.Goto, K.Beck, and Y.Kitagawa (1999).
A Drosophila gene encoding multiple splice variants of Kazal-type serine protease inhibitor-like proteins with potential destinations of mitochondria, cytosol and the secretory pathway.
  Eur J Biochem, 266, 282-292.  
  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
  9153250 B.Lenarcic, A.Ritonja, B.Strukelj, B.Turk, and V.Turk (1997).
Equistatin, a new inhibitor of cysteine proteinases from Actinia equina, is structurally related to thyroglobulin type-1 domain.
  J Biol Chem, 272, 13899-13903.  
9153400 G.F.Lee, R.A.Lazarus, and R.F.Kelley (1997).
Potent bifunctional anticoagulants: Kunitz domain-tissue factor fusion proteins.
  Biochemistry, 36, 5607-5611.  
9047335 G.T.DeKoster, and A.D.Robertson (1997).
Thermodynamics of unfolding for Kazal-type serine protease inhibitors: entropic stabilization of ovomucoid first domain by glycosylation.
  Biochemistry, 36, 2323-2331.  
9336216 J.Klingler, and T.Friedrich (1997).
Site-specific interaction of thrombin and inhibitors observed by fluorescence correlation spectroscopy.
  Biophys J, 73, 2195-2200.  
9242660 M.T.Stubbs, R.Morenweiser, J.Stürzebecher, M.Bauer, W.Bode, R.Huber, G.P.Piechottka, G.Matschiner, C.P.Sommerhoff, H.Fritz, and E.A.Auerswald (1997).
The three-dimensional structure of recombinant leech-derived tryptase inhibitor in complex with trypsin. Implications for the structure of human mast cell tryptase and its inhibition.
  J Biol Chem, 272, 19931-19937.
PDB code: 1ldt
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
9242661 R.Morenweiser, E.A.Auerswald, A.van de Locht, H.Fritz, J.Stürzebecher, and M.T.Stubbs (1997).
Structure-based design of a potent chimeric thrombin inhibitor.
  J Biol Chem, 272, 19938-19942.  
9384562 S.Di Marco, and J.P.Priestle (1997).
Structure of the complex of leech-derived tryptase inhibitor (LDTI) with trypsin and modeling of the LDTI-tryptase system.
  Structure, 5, 1465-1474.
PDB code: 1an1
8631941 A.van de Locht, M.T.Stubbs, M.Bauer, and W.Bode (1996).
Crystallographic evidence that the F2 kringle catalytic domain linker of prothrombin does not cover the fibrinogen recognition exosite.
  J Biol Chem, 271, 3413-3416.  
  8947023 A.van de Locht, M.T.Stubbs, W.Bode, T.Friedrich, C.Bollschweiler, W.Höffken, and R.Huber (1996).
The ornithodorin-thrombin crystal structure, a key to the TAP enigma?
  EMBO J, 15, 6011-6017.
PDB code: 1toc
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.

 

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