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PDBsum entry 2j4i
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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
2j4i

 

 

 

 

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Contents
Protein chains
232 a.a. *
52 a.a. *
Ligands
GSJ
Metals
_CA
Waters ×207
* Residue conservation analysis
PDB id:
2j4i
Name: Hydrolase
Title: Crystal structure of a human factor xa inhibitor complex
Structure: Coagulation factor x. Chain: a. Fragment: activated desgla, residues 235-488. Synonym: stuart factor, stuart-prower factor, activated factor xa heavy chain. Other_details: disulphide linked to other chain. Coagulation factor x. Chain: b. Fragment: activated desgla, residues 46-179.
Source: Homo sapiens. Human. Organism_taxid: 9606. Other_details: purchased from enzyme research labs. Isolated from human blood. Human blood
Biol. unit: Dimer (from PDB file)
Resolution:
1.80Å     R-factor:   0.192     R-free:   0.234
Authors: R.J.Young,M.Campbell,A.D.Borthwick,D.Brown,C.Chan,M.A.Convery, M.C.Crowe,S.Dayal,H.Diallo,H.A.Kelly,N.Paul King,S.Kleanthous, C.L.Kurtis,A.M.Mason,J.E.Mordaunt,C.Patel,A.J.Pateman,S.Senger, G.P.Shah,P.W.Smith,N.S.Watson,H.E.Weston,P.Zhou
Key ref: R.J.Young et al. (2006). Structure- and property-based design of factor Xa inhibitors: pyrrolidin-2-ones with acyclic alanyl amides as P4 motifs. Bioorg Med Chem Lett, 16, 5953-5957. PubMed id: 16982190 DOI: 10.1016/j.bmcl.2006.09.001
Date:
31-Aug-06     Release date:   27-Sep-06    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00742  (FA10_HUMAN) -  Coagulation factor X from Homo sapiens
Seq:
Struc: 		488 a.a.
232 a.a.
Protein chain
Pfam   ArchSchema ?
P00742  (FA10_HUMAN) -  Coagulation factor X from Homo sapiens
Seq:
Struc: 		488 a.a.
52 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.3.4.21.6  - coagulation factor Xa.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage: Arg-|-Thr and then Arg-|-Ile bonds in prothrombin to form thrombin.

 

 
DOI no: 10.1016/j.bmcl.2006.09.001 Bioorg Med Chem Lett 16:5953-5957 (2006)
PubMed id: 16982190  
 
 
Structure- and property-based design of factor Xa inhibitors: pyrrolidin-2-ones with acyclic alanyl amides as P4 motifs.
R.J.Young, M.Campbell, A.D.Borthwick, D.Brown, C.L.Burns-Kurtis, C.Chan, M.A.Convery, M.C.Crowe, S.Dayal, H.Diallo, H.A.Kelly, N.P.King, S.Kleanthous, A.M.Mason, J.E.Mordaunt, C.Patel, A.J.Pateman, S.Senger, G.P.Shah, P.W.Smith, N.S.Watson, H.E.Weston, P.Zhou.
 
  ABSTRACT  
 
Structure-based drug design was exploited in the synthesis of 3-(6-chloronaphth-2-ylsulfonyl)aminopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating an alanylamide P4 group with acyclic tertiary amide termini. Optimized hydrophobic contacts of one amide substituent in P4 were complemented by hydrophobicity-modulating features in the second, producing potent fXa inhibitors including examples with excellent anticoagulant properties.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19967784 Y.K.Lee, and M.R.Player (2011).
Developments in factor Xa inhibitors for the treatment of thromboembolic disorders.
  Med Res Rev, 31, 202-283.  
20345171 C.Bissantz, B.Kuhn, and M.Stahl (2010).
A medicinal chemist's guide to molecular interactions.
  J Med Chem, 53, 5061-5084.  
18645410 M.A.Abboud, S.J.Needle, C.L.Burns-Kurtis, R.E.Valocik, P.F.Koster, A.J.Amour, C.Chan, D.Brown, L.Chaudry, P.Zhou, A.Patikis, C.Patel, A.J.Pateman, R.J.Young, N.S.Watson, and J.R.Toomey (2008).
Antithrombotic potential of GW813893: a novel, orally active, active-site directed factor Xa inhibitor.
  J Cardiovasc Pharmacol, 52, 66-71.  
18266362 R.Abel, T.Young, R.Farid, B.J.Berne, and R.A.Friesner (2008).
Role of the active-site solvent in the thermodynamics of factor Xa ligand binding.
  J Am Chem Soc, 130, 2817-2831.  
17683371 J.T.Kohrt, C.F.Bigge, J.W.Bryant, A.Casimiro-Garcia, L.Chi, W.L.Cody, T.Dahring, D.A.Dudley, K.J.Filipski, S.Haarer, R.Heemstra, N.Janiczek, L.Narasimhan, T.McClanahan, J.T.Peterson, V.Sahasrabudhe, R.Schaum, C.A.Van Huis, K.M.Welch, E.Zhang, R.J.Leadley, and J.J.Edmunds (2007).
The discovery of (2R,4R)-N-(4-chlorophenyl)-N- (2-fluoro-4-(2-oxopyridin-1(2H)-yl)phenyl)-4-methoxypyrrolidine-1,2-dicarboxamide (PD 0348292), an orally efficacious factor Xa inhibitor.
  Chem Biol Drug Des, 70, 100-112.
PDB code: 2phb
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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