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PDBsum entry 1qb6
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protein ligands metals links
Hydrolase PDB id
1qb6

 

 

 

 

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Contents
Protein chain
223 a.a. *
Ligands
623
Metals
_CA
__K
Waters ×135
* Residue conservation analysis
PDB id:
1qb6
Name: Hydrolase
Title: Bovine trypsin 3,3'-[3,5-difluoro-4-methyl-2, 6-pyridinediylbis(oxy) ]bis(benzenecarboximidamide) (zk-805623) complex
Structure: Protein (trypsin). Chain: a. Fragment: bovine trypsin. Ec: 3.4.21.4
Source: Bos taurus. Cattle. Organism_taxid: 9913. Organ: pancreas. Other_details: boehringer mannheim catalog number 109,827
Resolution:
1.80Å     R-factor:   0.188     R-free:   0.224
Authors: M.Whitlow
Key ref:
M.Whitlow et al. (1999). Crystallographic analysis of potent and selective factor Xa inhibitors complexed to bovine trypsin. Acta Crystallogr D Biol Crystallogr, 55, 1395-1404. PubMed id: 10417407 DOI: 10.1107/S0907444999007350
Date:
29-Apr-99     Release date:   29-Apr-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
P00760  (TRY1_BOVIN) -  Serine protease 1 from Bos taurus
Seq:
Struc: 		246 a.a.
223 a.a.
Key:    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: 10.1107/S0907444999007350 Acta Crystallogr D Biol Crystallogr 55:1395-1404 (1999)
PubMed id: 10417407  
 
 
Crystallographic analysis of potent and selective factor Xa inhibitors complexed to bovine trypsin.
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, M.M.Morrissey.
 
  ABSTRACT  
 
Factor Xa is a serine protease which activates thrombin (factor IIa) and plays a key regulatory role in the blood-coagulation cascade. Factor Xa is, therefore, an important target for the design of anti-thrombotics. Both factor Xa and thrombin share sequence and structural homology with trypsin. As part of a factor Xa inhibitor-design program, a number of factor Xa inhibitors were crystallographically studied complexed to bovine trypsin. The structures of one diaryl benzimidazole, one diaryl carbazole and three diaryloxypyridines are described. All five compounds bind to trypsin in an extended conformation, with an amidinoaryl group in the S1 pocket and a second basic/hydrophobic moiety bound in the S4 pocket. These binding modes all bear a resemblance to the reported binding mode of DX-9065a in bovine trypsin and human factor Xa.
 
  Selected figure(s)  
 
Figure 5.
Figure 5 Superposition of bovine trypsin (I) and Daiichi's DX-9065a (PDB entry 1mtw) complexes. The C atoms of the inhibitor (I) and DX-9065a are colored green and blue, respectively. The majority of the C atoms in the trypsin bound to (I) are gray and those bound to DX-9065a are black. C atoms of specific residues have been colored. Asp189 (177) at the bottom of the S1 pocket is colored light blue. The catalytic triad Ser195 (183), His57 (46) and Asp102 (90), are colored orange. Residues which form the S4 pocket, Thr98 (86), Leu99 (87), Gln175 (161) and Trp215 (199), are colored purple. Hydrogen bonds are depicted as dashed lines. Hydrogen bonds to the naphthylamidine in DX-9065a have been omitted for clarity, as they are identical in both complexes. 		Figure 6.
Figure 6 Superposition of the bovine trypsin (V) and human factor Xa DX-9065a (PDB entry 1fax) complexes. The C atoms of the inhibitor (V) and DX-9065a are colored green and blue, respectively. The majority of the C atoms in trypsin are colored gray and in factor Xa are colored black. C atoms of the five amino-acid changes between bovine trypsin and human factor Xa (Asn/Asp97, Tyr/Leu99, Gln175/Phe174, Ser/Ala190 and Ser/Glu217) have been colored green in trypsin and purple in human factor Xa. The catalytic triad residues (Ser195, His57 and Asp102) in both structures are colored orange.
 
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (1999, 55, 1395-1404) copyright 1999.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19217394 A.R.Kinjo, and H.Nakamura (2009).
Comprehensive structural classification of ligand-binding motifs in proteins.
  Structure, 17, 234-246.  
15044735 H.K.Leiros, B.O.Brandsdal, O.A.Andersen, V.Os, I.Leiros, R.Helland, J.Otlewski, N.P.Willassen, and A.O.Smalås (2004).
Trypsin specificity as elucidated by LIE calculations, X-ray structures, and association constant measurements.
  Protein Sci, 13, 1056-1070.
PDB codes: 1utj 1utk 1utl 1utm 1utn 1uto 1utp 1utq
14517908 A.Nayeem, S.Krystek, and T.Stouch (2003).
An assessment of protein-ligand binding site polarizability.
  Biopolymers, 70, 201-211.  
10944388 V.Z.Pletnev, T.S.Zamolodchikova, W.A.Pangborn, and W.L.Duax (2000).
Crystal structure of bovine duodenase, a serine protease, with dual trypsin and chymotrypsin-like specificities.
  Proteins, 41, 8.
PDB code: 1euf
10853669 Z.Zhao, D.O.Arnaiz, B.Griedel, S.Sakata, J.L.Dallas, M.Whitlow, L.Trinh, J.Post, A.Liang, M.M.Morrissey, and K.J.Shaw (2000).
Design, synthesis, and in vitro biological activity of benzimidazole based factor Xa inhibitors.
  Bioorg Med Chem Lett, 10, 963-966.  
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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