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PDBsum entry 1bbr

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protein Protein-protein interface(s) links
Serine protease PDB id
1bbr
Jmol
Contents
Protein chains
36 a.a. *
150 a.a. *
109 a.a. *
11 a.a. *
259 a.a. *
Waters ×706
* Residue conservation analysis
PDB id:
1bbr
Name: Serine protease
Title: The structure of residues 7-16 of the a alpha chain of human fibrinogen bound to bovine thrombin at 2.3 angstroms resolution
Structure: Epsilon-thrombin. Chain: l, j, m. Engineered: yes. Epsilon-thrombin. Chain: h. Engineered: yes. Epsilon-thrombin. Chain: e. Engineered: yes.
Source: Bos taurus. Cattle. Organism_taxid: 9913. Homo sapiens. Human. Organism_taxid: 9606. Organism_taxid: 9913
Biol. unit: Trimer (from PQS)
Resolution:
2.30Å     R-factor:   0.167    
Authors: P.Martin,B.Edwards
Key ref: P.D.Martin et al. (1992). The structure of residues 7-16 of the A alpha-chain of human fibrinogen bound to bovine thrombin at 2.3-A resolution. J Biol Chem, 267, 7911-7920. PubMed id: 1560020
Date:
27-Apr-92     Release date:   31-Jan-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00735  (THRB_BOVIN) -  Prothrombin
Seq:
Struc:
 
Seq:
Struc:
625 a.a.
36 a.a.
Protein chain
Pfam   ArchSchema ?
P00735  (THRB_BOVIN) -  Prothrombin
Seq:
Struc:
 
Seq:
Struc:
625 a.a.
150 a.a.
Protein chain
Pfam   ArchSchema ?
P00735  (THRB_BOVIN) -  Prothrombin
Seq:
Struc:
 
Seq:
Struc:
625 a.a.
109 a.a.
Protein chains
Pfam   ArchSchema ?
P02671  (FIBA_HUMAN) -  Fibrinogen alpha chain
Seq:
Struc:
 
Seq:
Struc:
866 a.a.
10 a.a.
Protein chains
Pfam   ArchSchema ?
P00735  (THRB_BOVIN) -  Prothrombin
Seq:
Struc:
 
Seq:
Struc:
625 a.a.
259 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     blood coagulation   2 terms 
  Biochemical function     catalytic activity     3 terms  

 

 
J Biol Chem 267:7911-7920 (1992)
PubMed id: 1560020  
 
 
The structure of residues 7-16 of the A alpha-chain of human fibrinogen bound to bovine thrombin at 2.3-A resolution.
P.D.Martin, W.Robertson, D.Turk, R.Huber, W.Bode, B.F.Edwards.
 
  ABSTRACT  
 
The tetradecapeptide Ac-D-F-L-A-E-G-G-G-V-R-G-P-R-V-OMe, which mimics residues 7f-20f of the A alpha-chain of human fibrinogen, has been co-crystallized with bovine thrombin from ammonium sulfate solutions in space group P2(1) with unit cell dimensions of a = 83.0 A, b = 89.4 A, c = 99.3 A, and beta = 106.6 degrees. Three crystallographically independent complexes were located in the asymmetric unit by molecular replacement using the native bovine thrombin structure as a model. The standard crystallographic R-factor is 0.167 at 2.3-A resolution. Excellent electron density could be traced for the decapeptide, beginning with Asp-7f and ending with Arg-16f in the active site of thrombin; the remaining 4 residues, which have been cleaved from the tetradecapeptide at the Arg-16f/Gly-17f bond, are not seen. Residues 7f-11f at the NH2 terminus of the peptide form a single turn of alpha-helix that is connected by Gly-12f, which has a positive phi angle, to an extended chain containing residues 13f-16f. The major specific interactions between the peptide and thrombin are 1) a hydrophobic cage formed by residues Tyr-60A, Trp-60D, Leu-99, Ile-174, Trp-215, Leu-9f, Gly-13f, and Val-15f that surrounds Phe-8f; 2) a hydrogen bond linking Phe-8f NH to Lys-97 O;3) a salt link between Glu-11f and Arg-173; 4) two antiparallel beta-sheet hydrogen bonds between Gly-14f and Gly-216; and 5) the insertion of Arg-16f into the specificity pocket. Binding of the peptide is accompanied by a considerable shift in two of the loops near the active site relative to human D-phenyl-L-prolyl-L-arginyl chloromethyl ketone (PPACK)-thrombin.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20218626 M.A.Jadhav, G.Isetti, T.A.Trumbo, and M.C.Maurer (2010).
Effects of introducing fibrinogen Aalpha character into the factor XIII activation peptide segment.
  Biochemistry, 49, 2918-2924.  
19644995 C.Y.Koh, M.Kazimirova, P.A.Nuttall, and R.M.Kini (2009).
Noncompetitive inhibitor of thrombin.
  Chembiochem, 10, 2155-2158.  
19804366 M.D.Andersen, M.Kjalke, S.Bang, I.Lautrup-Larsen, P.Becker, A.S.Andersen, O.H.Olsen, and H.R.Stennicke (2009).
Coagulation factor XIII variants with altered thrombin activation rates.
  Biol Chem, 390, 1279-1283.  
19591434 T.M.Sabo, and M.C.Maurer (2009).
Biophysical investigation of GpIbalpha binding to thrombin anion binding exosite II.
  Biochemistry, 48, 7110-7122.  
16533041 I.Pechik, S.Yakovlev, M.W.Mosesson, G.L.Gilliland, and L.Medved (2006).
Structural basis for sequential cleavage of fibrinopeptides upon fibrin assembly.
  Biochemistry, 45, 3588-3597.
PDB code: 2a45
16230339 P.Panizzi, R.Friedrich, P.Fuentes-Prior, K.Richter, P.E.Bock, and W.Bode (2006).
Fibrinogen substrate recognition by staphylocoagulase.(pro)thrombin complexes.
  J Biol Chem, 281, 1179-1187.  
16102053 J.A.Huntington (2005).
Molecular recognition mechanisms of thrombin.
  J Thromb Haemost, 3, 1861-1872.  
15705787 K.Nogami, Q.Zhou, H.Wakabayashi, and P.J.Fay (2005).
Thrombin-catalyzed activation of factor VIII with His substituted for Arg372 at the P1 site.
  Blood, 105, 4362-4368.  
15892855 W.Bode (2005).
The structure of thrombin, a chameleon-like proteinase.
  J Thromb Haemost, 3, 2379-2388.  
15049836 G.Isetti, and M.C.Maurer (2004).
Probing thrombin's ability to accommodate a V34F substitution within the factor XIII activation peptide segment (28-41).
  J Pept Res, 63, 241-252.  
14978285 I.Pechik, J.Madrazo, M.W.Mosesson, I.Hernandez, G.L.Gilliland, and L.Medved (2004).
Crystal structure of the complex between thrombin and the central "E" region of fibrin.
  Proc Natl Acad Sci U S A, 101, 2718-2723.
PDB code: 1qvh
14567919 K.Ponnuraj, M.G.Bowden, S.Davis, S.Gurusiddappa, D.Moore, D.Choe, Y.Xu, M.Hook, and S.V.Narayana (2003).
A "dock, lock, and latch" structural model for a staphylococcal adhesin binding to fibrinogen.
  Cell, 115, 217-228.
PDB codes: 1r17 1r19
11969409 P.Ingallinella, D.Fattori, S.Altamura, C.Steinkühler, U.Koch, D.Cicero, R.Bazzo, R.Cortese, E.Bianchi, and A.Pessi (2002).
Prime site binding inhibitors of a serine protease: NS3/4A of hepatitis C virus.
  Biochemistry, 41, 5483-5492.  
11774230 G.R.Marshall (2001).
Peptide interactions with G-protein coupled receptors.
  Biopolymers, 60, 246-277.  
10694407 J.J.Slon-Usakiewicz, J.Sivaraman, Y.Li, M.Cygler, and Y.Konishi (2000).
Design of P1' and P3' residues of trivalent thrombin inhibitors and their crystal structures.
  Biochemistry, 39, 2384-2391.
PDB codes: 1eoj 1eol
10739913 R.Krishnan, J.E.Sadler, and A.Tulinsky (2000).
Structure of the Ser195Ala mutant of human alpha--thrombin complexed with fibrinopeptide A(7--16): evidence for residual catalytic activity.
  Acta Crystallogr D Biol Crystallogr, 56, 406-410.
PDB code: 1dm4
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.  
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
10336381 M.C.Maurer, J.Y.Trosset, C.C.Lester, E.E.DiBella, and H.A.Scheraga (1999).
New general approach for determining the solution structure of a ligand bound weakly to a receptor: structure of a fibrinogen Aalpha-like peptide bound to thrombin (S195A) obtained using NOE distance constraints and an ECEPP/3 flexible docking program.
  Proteins, 34, 29-48.  
10089499 C.L.Strickland, J.M.Fevig, R.A.Galemmo, B.L.Wells, C.A.Kettner, and P.C.Weber (1998).
Biochemical and crystallographic characterization of homologous non-peptidic thrombin inhibitors having alternate binding modes.
  Acta Crystallogr D Biol Crystallogr, 54, 1207-1215.  
9636031 C.Steinkühler, G.Biasiol, M.Brunetti, A.Urbani, U.Koch, R.Cortese, A.Pessi, and R.De Francesco (1998).
Product inhibition of the hepatitis C virus NS3 protease.
  Biochemistry, 37, 8899-8905.  
9772168 E.Skordalakes, S.Elgendy, C.A.Goodwin, D.Green, M.F.Scully, V.V.Kakkar, J.M.Freyssinet, G.Dodson, and J.J.Deadman (1998).
Bifunctional peptide boronate inhibitors of thrombin: crystallographic analysis of inhibition enhanced by linkage to an exosite 1 binding peptide.
  Biochemistry, 37, 14420-14427.
PDB codes: 1a3b 1a3e
9873562 I.Massova, P.Martin, A.Bulychev, R.Kocz, M.Doyle, B.F.Edwards, and S.Mobashery (1998).
Templates for design of inhibitors for serine proteases: application of the program DOCK to the discovery of novel inhibitors for thrombin.
  Bioorg Med Chem Lett, 8, 2463-2466.  
9558322 M.C.Maurer, J.L.Peng, S.S.An, J.Y.Trosset, A.Henschen-Edman, and H.A.Scheraga (1998).
Structural examination of the influence of phosphorylation on the binding of fibrinopeptide A to bovine thrombin.
  Biochemistry, 37, 5888-5902.  
9873610 M.Llinàs-Brunet, M.Bailey, R.Déziel, G.Fazal, V.Gorys, S.Goulet, T.Halmos, R.Maurice, M.Poirier, M.A.Poupart, J.Rancourt, D.Thibeault, D.Wernic, and D.Lamarre (1998).
Studies on the C-terminal of hexapeptide inhibitors of the hepatitis C virus serine protease.
  Bioorg Med Chem Lett, 8, 2719-2724.  
9753458 M.M.Rooney, J.L.Mullin, and S.T.Lord (1998).
Substitution of tyrosine for phenylalanine in fibrinopeptide A results in preferential thrombin cleavage of fibrinopeptide B from fibrinogen.
  Biochemistry, 37, 13704-13709.  
9636032 P.Ingallinella, S.Altamura, E.Bianchi, M.Taliani, R.Ingenito, R.Cortese, R.De Francesco, C.Steinkühler, and A.Pessi (1998).
Potent peptide inhibitors of human hepatitis C virus NS3 protease are obtained by optimizing the cleavage products.
  Biochemistry, 37, 8906-8914.  
9724521 R.Krishnan, E.Zhang, K.Hakansson, R.K.Arni, A.Tulinsky, M.S.Lim-Wilby, O.E.Levy, J.E.Semple, and T.K.Brunck (1998).
Highly selective mechanism-based thrombin inhibitors: structures of thrombin and trypsin inhibited with rigid peptidyl aldehydes.
  Biochemistry, 37, 12094-12103.
PDB codes: 1ba8 1bb0 1ca8 1yyy 1zzz
  9792427 S.Tada, and J.J.Blow (1998).
The replication licensing system.
  Biol Chem, 379, 941-949.  
9184147 A.Vindigni, C.E.White, E.A.Komives, and E.Di Cera (1997).
Energetics of thrombin-thrombomodulin interaction.
  Biochemistry, 36, 6674-6681.  
9235981 K.h.Hsieh (1997).
Localization of an effective fibrin beta-chain polymerization site: implications for the polymerization mechanism.
  Biochemistry, 36, 9381-9387.  
  9232645 M.G.Malkowski, P.D.Martin, J.C.Guzik, and B.F.Edwards (1997).
The co-crystal structure of unliganded bovine alpha-thrombin and prethrombin-2: movement of the Tyr-Pro-Pro-Trp segment and active site residues upon ligand binding.
  Protein Sci, 6, 1438-1448.
PDB codes: 1mkw 1mkx
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
9035139 Q.D.Dang, E.R.Guinto, and E.di Cera (1997).
Rational engineering of activity and specificity in a serine protease.
  Nat Biotechnol, 15, 146-149.  
9195869 U.Obst, D.W.Banner, L.Weber, and F.Diederich (1997).
Molecular recognition at the thrombin active site: structure-based design and synthesis of potent and selective thrombin inhibitors and the X-ray crystal structures of two thrombin-inhibitor complexes.
  Chem Biol, 4, 287-295.  
9022671 A.R.Rezaie, and C.T.Esmon (1996).
Molecular basis of residue 192 participation in determination of coagulation protease specificity.
  Eur J Biochem, 242, 477-484.  
8605191 A.Vindigni, and E.Di Cera (1996).
Release of fibrinopeptides by the slow and fast forms of thrombin.
  Biochemistry, 35, 4417-4426.  
8689236 D.C.Horwell, W.Howson, G.S.Ratcliffe, and H.M.Willems (1996).
The design of dipeptide helical mimetics: the synthesis, tachykinin receptor affinity and conformational analysis of 1,1,6-trisubstituted indanes.
  Bioorg Med Chem, 4, 33-42.  
8679942 F.Ni, K.A.Carpenter, D.R.Ripoll, S.D.Sanderson, and T.E.Hugli (1996).
Stabilization of an isolated helical capping box in solution by hydrophobic interactions: evidence from the NMR study of bioactive peptides from the C-terminus of human C5a anaphylatoxin.
  Biopolymers, 38, 31-41.  
8924207 P.D.Boxrud, and L.J.Berliner (1996).
Comparison of the active-site conformations of bovine alpha-thrombin and meizothrombin(desF1) by electron spin resonance.
  J Protein Chem, 15, 231-242.  
8786410 P.D.Grootenhuis, and M.Karplus (1996).
Functionality map analysis of the active site cleft of human thrombin.
  J Comput Aided Mol Des, 10, 1.  
8855938 P.D.Martin, M.G.Malkowski, J.DiMaio, Y.Konishi, F.Ni, and B.F.Edwards (1996).
Bovine thrombin complexed with an uncleavable analog of residues 7-19 of fibrinogen A alpha: geometry of the catalytic triad and interactions of the P1', P2', and P3' substrate residues.
  Biochemistry, 35, 13030-13039.
PDB code: 1ucy
  8868478 R.Krishnan, A.Tulinsky, G.P.Vlasuk, D.Pearson, P.Vallar, P.Bergum, T.K.Brunck, and W.C.Ripka (1996).
Synthesis, structure, and structure-activity relationships of divalent thrombin inhibitors containing an alpha-keto-amide transition-state mimetic.
  Protein Sci, 5, 422-433.
PDB code: 1dit
8652575 S.T.Lord, E.Strickland, and E.Jayjock (1996).
Strategy for recombinant multichain protein synthesis: fibrinogen B beta-chain variants as thrombin substrates.
  Biochemistry, 35, 2342-2348.  
8703940 V.L.Nienaber, L.J.Mersinger, and C.A.Kettner (1996).
Structure-based understanding of ligand affinity using human thrombin as a model system.
  Biochemistry, 35, 9690-9699.  
7878739 M.T.Stubbs, and W.Bode (1995).
The clot thickens: clues provided by thrombin structure.
  Trends Biochem Sci, 20, 23-28.  
7582978 W.F.Lau, L.Tabernero, J.S.Sack, and E.J.Iwanowicz (1995).
Molecular modeling studies of novel retro-binding tripeptide active-site inhibitors of thrombin.
  Bioorg Med Chem, 3, 1039-1048.  
8202520 J.P.Sheehan, and J.E.Sadler (1994).
Molecular mapping of the heparin-binding exosite of thrombin.
  Proc Natl Acad Sci U S A, 91, 5518-5522.  
8112314 M.Picozzi, R.Landolfi, and R.De Cristofaro (1994).
Effects of protons on the thrombin-fibrinogen interaction.
  Eur J Biochem, 219, 1013-1021.  
7712286 M.T.Stubbs, and W.Bode (1994).
Coagulation factors and their inhibitors.
  Curr Opin Struct Biol, 4, 823-832.  
8272424 A.Zdanov, S.Wu, J.DiMaio, Y.Konishi, Y.Li, X.Wu, B.F.Edwards, P.D.Martin, and M.Cygler (1993).
Crystal structure of the complex of human alpha-thrombin and nonhydrolyzable bifunctional inhibitors, hirutonin-2 and hirutonin-6.
  Proteins, 17, 252-265.
PDB codes: 1ihs 1iht
8296393 C.Tapparelli, R.Metternich, C.Ehrhardt, and N.S.Cook (1993).
Synthetic low-molecular weight thrombin inhibitors: molecular design and pharmacological profile.
  Trends Pharmacol Sci, 14, 366-376.  
  8251938 J.P.Priestle, J.Rahuel, H.Rink, M.Tones, and M.G.Grütter (1993).
Changes in interactions in complexes of hirudin derivatives and human alpha-thrombin due to different crystal forms.
  Protein Sci, 2, 1630-1642.
PDB codes: 1tmt 1tmu
8393788 M.C.Bouton, M.Jandrot-Perrus, A.Bezeaud, and M.C.Guillin (1993).
Late-fibrin(ogen) fragment E modulates human alpha-thrombin specificity.
  Eur J Biochem, 215, 143-149.  
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.