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PDBsum entry 2j95
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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
2j95

 

 

 

 

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Contents
Protein chains
234 a.a. *
52 a.a. *
Ligands
GSX
Metals
_CA
Waters ×168
* Residue conservation analysis
PDB id:
2j95
Name: Hydrolase
Title: Crystal structure of a human factor xa inhibitor complex
Structure: Activated factor xa heavy chain. Chain: a. Fragment: activated desgla, residues 235-488. Synonym: stuart factor, stuart-prower factor. Other_details: disulphide linked to other chain. Activated factor xa light chain. Chain: b. Fragment: activated desgla, residues 46-179. Synonym: stuart factor, stuart-prower factor.
Source: Homo sapiens. Human. Organism_taxid: 9606. Other_details: purchased from enzyme research labs. Isolated from human blood. Human blood
Resolution:
2.01Å     R-factor:   0.195     R-free:   0.242
Authors: C.Chan,A.D.Borthwick,D.Brown,M.Campbell,L.Chaudry,C.W.Chung, M.A.Convery,J.N.Hamblin,L.Johnstone,H.A.Kelly,S.Kleanthous, C.L.Burns-Kurtis,A.Patikis,C.Patel,A.J.Pateman,S.Senger,G.P.Shah, J.R.Toomey,N.S.Watson,H.E.Weston,C.Whitworth,R.J.Young,P.Zhou
Key ref: C.Chan et al. (2007). Factor Xa inhibitors: S1 binding interactions of a series of N-{(3S)-1-[(1S)-1-methyl-2-morpholin-4-yl-2-oxoethyl]-2-oxopyrrolidin-3-yl}sulfonamides. J Med Chem, 50, 1546-1557. PubMed id: 17338508 DOI: 10.1021/jm060870c
Date:
02-Nov-06     Release date:   20-Mar-07    
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.
234 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: 10.1021/jm060870c J Med Chem 50:1546-1557 (2007)
PubMed id: 17338508  
 
 
Factor Xa inhibitors: S1 binding interactions of a series of N-{(3S)-1-[(1S)-1-methyl-2-morpholin-4-yl-2-oxoethyl]-2-oxopyrrolidin-3-yl}sulfonamides.
C.Chan, A.D.Borthwick, D.Brown, C.L.Burns-Kurtis, M.Campbell, L.Chaudry, C.W.Chung, M.A.Convery, J.N.Hamblin, L.Johnstone, H.A.Kelly, S.Kleanthous, A.Patikis, C.Patel, A.J.Pateman, S.Senger, G.P.Shah, J.R.Toomey, N.S.Watson, H.E.Weston, C.Whitworth, R.J.Young, P.Zhou.
 
  ABSTRACT  
 
Factor Xa inhibitory activities for a series of N-{(3S)-1-[(1S)-1-methyl-2-morpholin-4-yl-2-oxoethyl]-2-oxopyrrolidin-3-yl}sulfonamides with different P1 groups are described. These data provide insight into binding interactions within the S1 primary specificity pocket; rationales are presented for the derived SAR on the basis of electronic interactions through crystal structures of fXa-ligand complexes and molecular modeling studies. A good correlation between in vitro anticoagulant activities with lipophilicity and the extent of human serum albumin binding is observed within this series of potent fXa inhibitors. Pharmacokinetic profiles in rat and dog, together with selectivity over other trypsin-like serine proteases, identified 1f as a candidate for further evaluation.
 

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.  
20953472 H.G.Wallnoefer, T.Fox, K.R.Liedl, and C.S.Tautermann (2010).
Dispersion dominated halogen-π interactions: energies and locations of minima.
  Phys Chem Chem Phys, 12, 14941-14949.  
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.  
18077174 Y.Imaeda, T.Miyawaki, H.Sakamoto, F.Itoh, N.Konishi, K.Hiroe, M.Kawamura, T.Tanaka, and K.Kubo (2008).
Discovery of sulfonylalkylamides: A new class of orally active factor Xa inhibitors.
  Bioorg Med Chem, 16, 2243-2260.  
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.

 

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