spacer
spacer

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

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chains
28 a.a. *
251 a.a. *
Ligands
ASP-PHE-GLU-GLU-
ILE-PRO-GLU-GLU-
TYS-LEU
APA
Waters ×231
* Residue conservation analysis
PDB id:
1aht
Name: Hydrolase/hydrolase inhibitor
Title: Crystal structure of human alpha-thrombin complexed with hirugen and p-amidinophenylpyruvate at 1.6 angstroms resolution
Structure: Alpha-thrombin (small subunit). Chain: l. Alpha-thrombin (large subunit). Chain: h. Hirugen. Chain: i
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: plasma.
Biol. unit: Hexamer (from PQS)
Resolution:
1.60Å     R-factor:   0.187    
Authors: Z.Chen
Key ref: Z.Chen et al. (1995). Crystal structure of human alpha-thrombin complexed with hirugen and p-amidinophenylpyruvate at 1.6 A resolution. Arch Biochem Biophys, 322, 198-203. PubMed id: 7574675
Date:
17-Mar-95     Release date:   17-Mar-96    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00734  (THRB_HUMAN) -  Prothrombin from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		622 a.a.
28 a.a.
Protein chain
Pfam   ArchSchema ?
P00734  (THRB_HUMAN) -  Prothrombin from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		622 a.a.
251 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains L, 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.

 

 
Arch Biochem Biophys 322:198-203 (1995)
PubMed id: 7574675  
 
 
Crystal structure of human alpha-thrombin complexed with hirugen and p-amidinophenylpyruvate at 1.6 A resolution.
Z.Chen, Y.Li, A.M.Mulichak, S.D.Lewis, J.A.Shafer.
 
  ABSTRACT  
 
Crystals of human alpha-thrombin complexed with hirugen and the alpha-keto acid thrombin inhibitor APPA (p-amidinophenylpyruvate) that diffract to 1.6 A resolution were obtained by soaking an alpha-thrombin-hirugen crystal in a solution of APPA. The crystal structure was determined using the difference Fourier method and refined to an R factor of 18.7% at 1.6 A resolution. This structure is the highest resolution structure of the thrombin molecule that is currently available. With the exception of the region near Arg77A-Asn78, the structures of the thrombin and hirugen molecules in the ternary complex are similar to those reported for the thrombin-hirugen binary complex. As previously determined for the APPA-trypsin complex, the carbonyl carbon atom of APPA forms a covalent bond with O gamma of Ser195 of thrombin to yield a "transition-state" analog of the tetrahedral intermediate. Comparison of the specificity pocket of the APPA complexes of thrombin and trypsin reveals differences in hydrogen bonding and shows for the first time that the S1 site of thrombin is larger than that of trypsin and as a result thrombin may be able to accommodate a bulkier P1 group than trypsin.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20148287 O.Nicolotti, I.Giangreco, T.F.Miscioscia, M.Convertino, F.Leonetti, L.Pisani, and A.Carotti (2010).
Screening of benzamidine-based thrombin inhibitors via a linear interaction energy in continuum electrostatics model.
  J Comput Aided Mol Des, 24, 117-129.  
19523945 Y.Kanan, A.Hoffhines, A.Rauhauser, A.Murray, and M.R.Al-Ubaidi (2009).
Protein tyrosine-O-sulfation in the retina.
  Exp Eye Res, 89, 559-567.  
17685615 C.C.Liu, E.Brustad, W.Liu, and P.G.Schultz (2007).
Crystal structure of a biosynthetic sulfo-hirudin complexed to thrombin.
  J Am Chem Soc, 129, 10648-10649.
PDB code: 2pw8
17372355 M.Sherawat, P.Kaur, M.Perbandt, C.Betzel, W.A.Slusarchyk, G.S.Bisacchi, C.Chang, B.L.Jacobson, H.M.Einspahr, and T.P.Singh (2007).
Structure of the complex of trypsin with a highly potent synthetic inhibitor at 0.97 A resolution.
  Acta Crystallogr D Biol Crystallogr, 63, 500-507.
PDB code: 2ayw
16428384 L.A.Bush, R.W.Nelson, and E.Di Cera (2006).
Murine thrombin lacks Na+ activation but retains high catalytic activity.
  J Biol Chem, 281, 7183-7188.  
16294249 C.Salvagnini, C.Michaux, J.Remiche, J.Wouters, P.Charlier, and J.Marchand-Brynaert (2005).
Design, synthesis and evaluation of graftable thrombin inhibitors for the preparation of blood-compatible polymer materials.
  Org Biomol Chem, 3, 4209-4220.
PDB code: 1w7g
11170379 U.Koch, G.Biasiol, M.Brunetti, D.Fattori, M.Pallaoro, and C.Steinkühler (2001).
Role of charged residues in the catalytic mechanism of hepatitis C virus NS3 protease: electrostatic precollision guidance and transition-state stabilization.
  Biochemistry, 40, 631-640.  
11134922 W.R.Rypniewski, P.R.Ostergaard, M.Nørregaard-Madsen, M.Dauter, and K.S.Wilson (2001).
Fusarium oxysporum trypsin at atomic resolution at 100 and 283 K: a study of ligand binding.
  Acta Crystallogr D Biol Crystallogr, 57, 8.
PDB codes: 1fn8 1fy4 1fy5 1gdn 1gdq 1gdu
10677236 F.Narjes, M.Brunetti, S.Colarusso, B.Gerlach, U.Koch, G.Biasiol, D.Fattori, R.De Francesco, V.G.Matassa, and C.Steinkühler (2000).
Alpha-ketoacids are potent slow binding inhibitors of the hepatitis C virus NS3 protease.
  Biochemistry, 39, 1849-1861.  
10716920 G.Barbato, D.O.Cicero, F.Cordier, F.Narjes, B.Gerlach, S.Sambucini, S.Grzesiek, V.G.Matassa, R.De Francesco, and R.Bazzo (2000).
Inhibitor binding induces active site stabilization of the HCV NS3 protein serine protease domain.
  EMBO J, 19, 1195-1206.
PDB code: 1dxw
10702283 S.Di Marco, M.Rizzi, C.Volpari, M.A.Walsh, F.Narjes, S.Colarusso, R.De Francesco, V.G.Matassa, and M.Sollazzo (2000).
Inhibition of the hepatitis C virus NS3/4A protease. The crystal structures of two protease-inhibitor complexes.
  J Biol Chem, 275, 7152-7157.
PDB codes: 1dxp 1dy8 1dy9
10329783 S.J.Liu, Q.Q.Huang, X.Y.Zhu, M.K.Teng, and L.W.Niu (1999).
Purification, characterization, crystallization and preliminary X-ray diffraction of acuthrombin-B, a thrombin-like enzyme from Agkistrodon acutus venom.
  Acta Crystallogr D Biol Crystallogr, 55, 1193-1197.  
9873418 A.M.Naylor-Olsen, G.S.Ponticello, S.D.Lewis, A.M.Mulichak, Z.Chen, C.N.Habecker, B.T.Phillips, W.M.Sanders, T.J.Tucker, J.A.Shafer, and J.P.Vacca (1998).
Identification and SAR for a selective, nonpeptidyl thrombin inhibitor.
  Bioorg Med Chem Lett, 8, 1697-1702.  
9618463 K.Kamata, H.Kawamoto, T.Honma, T.Iwama, and S.H.Kim (1998).
Structural basis for chemical inhibition of human blood coagulation factor Xa.
  Proc Natl Acad Sci U S A, 95, 6630-6635.
PDB codes: 1xka 1xkb
9871547 P.E.Sanderson, K.J.Cutrona, B.D.Dorsey, D.L.Dyer, C.M.McDonough, A.M.Naylor-Olsen, I.W.Chen, Z.Chen, J.J.Cook, S.J.Gardell, J.A.Krueger, S.D.Lewis, J.H.Lin, B.J.Lucas, E.A.Lyle, J.J.Lynch, M.T.Stranieri, K.Vastag, J.A.Shafer, and J.P.Vacca (1998).
L-374,087, an efficacious, orally bioavailable, pyridinone acetamide thrombin inhibitor.
  Bioorg Med Chem Lett, 8, 817-822.  
9478925 S.D.Lewis, B.J.Lucas, S.F.Brady, J.T.Sisko, K.J.Cutrona, P.E.Sanderson, R.M.Freidinger, S.S.Mao, S.J.Gardell, and J.A.Shafer (1998).
Characterization of the two-step pathway for inhibition of thrombin by alpha-ketoamide transition state analogs.
  J Biol Chem, 273, 4843-4854.  
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