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PDBsum entry 1mts
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Serine proteinase PDB id
1mts

 

 

 

 

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Contents
Protein chain
223 a.a. *
Ligands
BX3
Metals
_CA
Waters ×162
* Residue conservation analysis
PDB id:
1mts
Name: Serine proteinase
Title: Factor xa specific inhibitor in complex with bovine trypsin
Structure: Trypsin. Chain: a. Ec: 3.4.21.4
Source: Bos taurus. Cattle. Organism_taxid: 9913
Resolution:
1.90Å     R-factor:   0.179    
Authors: M.T.Stubbs
Key ref: M.T.Stubbs et al. (1995). Crystal structures of factor Xa specific inhibitors in complex with trypsin: structural grounds for inhibition of factor Xa and selectivity against thrombin. FEBS Lett, 375, 103-107. PubMed id: 7498454 DOI: 10.1016/0014-5793(95)01190-P
Date:
16-May-97     Release date:   20-Aug-97    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00760  (TRY1_BOVIN) -  Serine protease 1 from Bos taurus
Seq:
Struc: 		246 a.a.
223 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.4.21.4  - trypsin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.

 

 
DOI no: 10.1016/0014-5793(95)01190-P FEBS Lett 375:103-107 (1995)
PubMed id: 7498454  
 
 
Crystal structures of factor Xa specific inhibitors in complex with trypsin: structural grounds for inhibition of factor Xa and selectivity against thrombin.
M.T.Stubbs, R.Huber, W.Bode.
 
  ABSTRACT  
 
Crystal structures of DX9065a and a related bisamidino-aryl inhibitor specific for the blood-clotting factor Xa have been solved in complex with bovine beta-trypsin to a resolution of 1.9 A. Each inhibitor exhibits an extended conformation along the active site, in contrast to the compact folded structures observed for thrombin specific inhibitors. Few direct contacts (predominantly in the S1 pocket) are made between trypsin and the inhibitors. Transfer of the inhibitors to the active site of factor Xa suggests a three-site interaction: salt bridge formation at the base of the primary specificity pocket, extensive hydrophobic surface burial and a weak electrostatic interaction between the distal basic component of the inhibitor and an electronegative cavity of factor Xa formed by three backbone carbonyl oxygens. Additivity of these three interactions is the basis for the observed strong inhibition of factor Xa and provides a framework for the design of novel factor Xa inhibitors. A propionic acid group of the inhibitor would clash with the thrombin specific '60-insertion loop', thus conferring selectivity against thrombin.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20868223 D.R.Carrillo, C.Parthier, N.Jänckel, J.Grandke, M.Stelter, S.Schilling, M.Boehme, P.Neumann, R.Wolf, H.U.Demuth, M.T.Stubbs, and J.U.Rahfeld (2010).
Kinetic and structural characterization of bacterial glutaminyl cyclases from Zymomonas mobilis and Myxococcus xanthus.
  Biol Chem, 391, 1419-1428.
PDB codes: 3nok 3nol 3nom
17191291 A.Di Fenza, A.Heine, U.Koert, and G.Klebe (2007).
Understanding Binding Selectivity toward Trypsin and Factor Xa: the Role of Aromatic Interactions.
  ChemMedChem, 2, 297-308.
PDB codes: 1y59 1y5a 1y5b 1y5u
15632114 Z.Zhu, Z.Liang, T.Zhang, Z.Zhu, W.Xu, M.Teng, and L.Niu (2005).
Crystal structures and amidolytic activities of two glycosylated snake venom serine proteinases.
  J Biol Chem, 280, 10524-10529.
PDB codes: 1op0 1op2
15250038 C.A.Kontogiorgis, and D.Hadjipavlou-Litina (2004).
Current trends in quantitative structure activity relationships on FXa inhibitors: evaluation and comparative analysis.
  Med Res Rev, 24, 687-747.  
12437122 D.Rauh, S.Reyda, G.Klebe, and M.T.Stubbs (2002).
Trypsin mutants for structure-based drug design: expression, refolding and crystallisation.
  Biol Chem, 383, 1309-1314.  
12437104 M.M.Mueller, S.Sperl, J.Stürzebecher, W.Bode, and L.Moroder (2002).
(R)-3-Amidinophenylalanine-derived inhibitors of factor Xa with a novel active-site binding mode.
  Biol Chem, 383, 1185-1191.
PDB codes: 1kye 3liw
11296285 N.E.Robinson, and A.B.Robinson (2001).
Prediction of protein deamidation rates from primary and three-dimensional structure.
  Proc Natl Acad Sci U S A, 98, 4367-4372.  
10839461 S.Sperl, A.Bergner, J.Stürzebecher, V.Magdolen, W.Bode, and L.Moroder (2000).
Urethanyl-3-amidinophenylalanine derivatives as inhibitors of factor Xa. X-ray crystal structure of a trypsin/inhibitor complex and modeling studies.
  Biol Chem, 381, 321-329.  
10801494 V.L.Nienaber, D.Davidson, R.Edalji, V.L.Giranda, V.Klinghofer, J.Henkin, P.Magdalinos, R.Mantei, S.Merrick, J.M.Severin, R.A.Smith, K.Stewart, K.Walter, J.Wang, M.Wendt, M.Weitzberg, X.Zhao, and T.Rockway (2000).
Structure-directed discovery of potent non-peptidic inhibitors of human urokinase that access a novel binding subsite.
  Structure, 8, 553-563.  
10022353 M.S.Rao, and A.J.Olson (1999).
Modelling of factor Xa-inhibitor complexes: a computational flexible docking approach.
  Proteins, 34, 173-183.  
10417407 M.Whitlow, D.O.Arnaiz, B.O.Buckman, D.D.Davey, B.Griedel, W.J.Guilford, S.K.Koovakkat, A.Liang, R.Mohan, G.B.Phillips, M.Seto, K.J.Shaw, W.Xu, Z.Zhao, D.R.Light, and M.M.Morrissey (1999).
Crystallographic analysis of potent and selective factor Xa inhibitors complexed to bovine trypsin.
  Acta Crystallogr D Biol Crystallogr, 55, 1395-1404.
PDB codes: 1qa0 1qb1 1qb6 1qb9 1qbn 1qbo
10440994 Y.Zhou, and M.E.Johnson (1999).
Comparative molecular modeling analysis of-5-amidinoindole and benzamidine binding to thrombin and trypsin: specific H-bond formation contributes to high 5-amidinoindole potency and selectivity for thrombin and factor Xa.
  J Mol Recognit, 12, 235-241.  
9517542 F.Fraternali, Q.T.Do, B.T.Doan, R.A.Atkinson, P.Palmas, V.Sklenar, P.Safar, P.Wildgoose, P.Strop, and V.Saudek (1998).
Mapping the active site of factor Xa by selective inhibitors: an NMR and MD study.
  Proteins, 30, 264-274.  
9362477 K.P.Hopfner, H.Brandstetter, A.Karcher, E.Kopetzki, R.Huber, R.A.Engh, and W.Bode (1997).
Converting blood coagulation factor IXa into factor Xa: dramatic increase in amidolytic activity identifies important active site determinants.
  EMBO J, 16, 6626-6635.  
9268299 M.Renatus, W.Bode, R.Huber, J.Stürzebecher, D.Prasa, S.Fischer, U.Kohnert, and M.T.Stubbs (1997).
Structural mapping of the active site specificity determinants of human tissue-type plasminogen activator. Implications for the design of low molecular weight substrates and inhibitors.
  J Biol Chem, 272, 21713-21719.
PDB code: 1a5h
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
  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
8679610 J.A.Huntington, S.T.Olson, B.Fan, and P.G.Gettins (1996).
Mechanism of heparin activation of antithrombin. Evidence for reactive center loop preinsertion with expulsion upon heparin binding.
  Biochemistry, 35, 8495-8503.  
8939759 R.A.Engh, H.Brandstetter, G.Sucher, A.Eichinger, U.Baumann, W.Bode, R.Huber, T.Poll, R.Rudolph, and W.von der Saal (1996).
Enzyme flexibility, solvent and 'weak' interactions characterize thrombin-ligand interactions: implications for drug design.
  Structure, 4, 1353-1362.
PDB codes: 1uvs 1uvt 1uvu
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.

 

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