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PDBsum entry 2aei

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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
2aei
Jmol
Contents
Protein chains
142 a.a. *
254 a.a. *
195 a.a. *
Ligands
CAC
03R
Metals
_CA ×8
Waters ×81
* Residue conservation analysis
PDB id:
2aei
Name: Hydrolase
Title: Crystal structure of a ternary complex of factor viia/tissue and 2-[[6-[3-(aminoiminomethyl)phenoxy]-3,5-difluro-4-[(1-m phenylpropyl)amino]-2-pyridinyl]oxy]-benzoic acid
Structure: Coagulation factor vii. Chain: l. Fragment: light chain. Synonym: serum prothrombin conversion accelerator, spca, proconvertin, eptacog alfa. Engineered: yes. Coagulation factor vii. Chain: h. Fragment: heavy chain.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: f7. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_organ: kidney. Gene: f3. Expressed in: saccharomyces cerevisiae.
Biol. unit: Trimer (from PQS)
Resolution:
2.52Å     R-factor:   0.199     R-free:   0.297
Authors: M.Adler,M.Whitlow
Key ref: J.T.Kohrt et al. (2005). The discovery of fluoropyridine-based inhibitors of the Factor VIIa/TF complex. Bioorg Med Chem Lett, 15, 4752-4756. PubMed id: 16125385 DOI: 10.1016/j.bmcl.2005.07.059
Date:
22-Jul-05     Release date:   01-Aug-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P08709  (FA7_HUMAN) -  Coagulation factor VII
Seq:
Struc:
466 a.a.
142 a.a.*
Protein chain
Pfam   ArchSchema ?
P08709  (FA7_HUMAN) -  Coagulation factor VII
Seq:
Struc:
466 a.a.
254 a.a.
Protein chain
Pfam   ArchSchema ?
P13726  (TF_HUMAN) -  Tissue factor
Seq:
Struc:
295 a.a.
195 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 10 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains L, H: E.C.3.4.21.21  - Coagulation factor VIIa.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolyzes one Arg-|-Ile bond in factor X to form factor Xa.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     blood coagulation   2 terms 
  Biochemical function     catalytic activity     3 terms  

 

 
DOI no: 10.1016/j.bmcl.2005.07.059 Bioorg Med Chem Lett 15:4752-4756 (2005)
PubMed id: 16125385  
 
 
The discovery of fluoropyridine-based inhibitors of the Factor VIIa/TF complex.
J.T.Kohrt, K.J.Filipski, W.L.Cody, C.Cai, D.A.Dudley, C.A.Van Huis, J.A.Willardsen, S.T.Rapundalo, K.Saiya-Cork, R.J.Leadley, L.Narasimhan, E.Zhang, M.Whitlow, M.Adler, K.McLean, Y.L.Chou, C.McKnight, D.O.Arnaiz, K.J.Shaw, D.R.Light, J.J.Edmunds.
 
  ABSTRACT  
 
The activated Factor VII/tissue factor complex (FVIIa/TF) plays a key role in the formation of blood clots. Inhibition of this complex may lead to new antithrombotic drugs. An X-ray crystal structure of a fluoropyridine-based FVIIa/TF inhibitor bound in the active site of the enzyme complex suggested that incorporation of substitution at the 5-position of the hydroxybenzoic acid side chain could lead to the formation of more potent inhibitors through interactions with the S1'/S2' pocket.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
17505107 R.Krishnan, P.L.Kotian, P.Chand, S.Bantia, S.Rowland, and Y.S.Babu (2007).
Probing the S2 site of factor VIIa to generate potent and selective inhibitors: the structure of BCX-3607 in complex with tissue factor-factor VIIa.
  Acta Crystallogr D Biol Crystallogr, 63, 689-697.
PDB code: 2ec9
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.