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PDBsum entry 2zzu

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protein ligands metals Protein-protein interface(s) links
Hydrolase/blood clotting PDB id
2zzu
Jmol
Contents
Protein chains
142 a.a. *
254 a.a. *
191 a.a. *
Ligands
BGC
FUC
359
Metals
_CA ×9
Waters ×362
* Residue conservation analysis
PDB id:
2zzu
Name: Hydrolase/blood clotting
Title: Human factor viia-tissue factor complexed with ethylsulfonam (3-carboxybenzyloxy)-trp-gln-p-aminobenzamidine
Structure: Factor vii light chain. Chain: l. Fragment: unp residues 61-212. Synonym: serum prothrombin conversion accelerator, spca, proconvertin. Engineered: yes. Factor vii heavy chain. Chain: h. Fragment: unp residues 213-466.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: f7. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell: cho. Gene: f3. Expressed in: escherichia coli.
Resolution:
2.50Å     R-factor:   0.221     R-free:   0.273
Authors: S.Kadono,A.Sakamoto,Y.Kikuchi,M.Oh-Eda,N.Yabuta,T.Koga,K.Hat T.Shiraishi,M.Haramura,H.Sato,M.Ohta,T.Kozono
Key ref: T.Shiraishi et al. (2010). Design and synthesis of peptidomimetic factor VIIa inhibitors. Chem Pharm Bull (Tokyo), 58, 38-44. PubMed id: 20045964
Date:
25-Feb-09     Release date:   24-Mar-09    
PROCHECK
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 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.
191 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  

 

 
Chem Pharm Bull (Tokyo) 58:38-44 (2010)
PubMed id: 20045964  
 
 
Design and synthesis of peptidomimetic factor VIIa inhibitors.
T.Shiraishi, S.Kadono, M.Haramura, H.Kodama, Y.Ono, H.Iikura, T.Esaki, T.Koga, K.Hattori, Y.Watanabe, A.Sakamoto, K.Yoshihashi, T.Kitazawa, K.Esaki, M.Ohta, H.Sato, T.Kozono.
 
  ABSTRACT  
 
Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is regarded as a promising target for developing new anticoagulant drugs. In previous reports, we described a S3 subsite found in the X-ray crystal structure of compound 2 that bound to FVIIa/soluble tissue factor (sTF). Based on the X-ray crystal structure information and with the aim of improving the inhibition activity for FVIIa/TF and selectivity against other serine proteases, we synthesized derivatives by introducing substituents at position 5 of the indole ring of compound 2. Among them, compound 16 showed high selectivity against other serine proteases. Contrary to our expectations, compound 16 did not occupy the S3-subsite; X-ray structure analysis revealed that compound 16 improved selectivity by forming hydrogen bonds with Gln217, Thr99 and Asn100.