PDBsum entry: 1wv7

Hydrolase/blood clotting

PDB id: 1wv7

Contents

Protein chains

142 a.a. *

254 a.a. *

191 a.a. *

Ligands

BGC

FUC

5PI

Metals

_CA ×9

Waters ×289

* Residue conservation analysis

PDB id:

1wv7

Name:

Hydrolase/blood clotting

Title:

Human factor viia-tissue factor complexed with ethylsulfonamide-d-5-propoxy-trp-gln-p-aminobenzamidine

Structure:

Coagulation factor vii. Chain: l. Fragment: factor vii light chain. Synonym: serum prothrombin conversion accelerator, spca, proconvertin, eptacog alfa. Engineered: yes. Coagulation factor vii. Chain: h. Fragment: factor vii heavy chain.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell: cho. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Trimer (from PQS)

Resolution:

2.70Å R-factor: 0.226 R-free: 0.273

Authors:

S.Kadono,A.Sakamoto,Y.Kikuchi,M.Oh-Eda,N.Yabuta, K.Yoshihashi,T.Kitazawa,T.Suzuki,T.Koga,K.Hattori, T.Shiraishi,M.Haramura,H.Kodama,Y.Ono,T.Esaki,H.Sato, Y.Watanabe,S.Itoh,M.Ohta,T.Kozono

Key ref:

S.Kadono et al. (2005). Structure-based design of P3 moieties in the peptide mimetic factor VIIa inhibitor. Biochem Biophys Res Commun, 327, 589-596. PubMed id: 15629154 DOI: 10.1016/j.bbrc.2004.12.042

Date:

11-Dec-04 Release date: 11-Dec-05

Protein chain

P08709  (FA7_HUMAN) -  Coagulation factor VII

Seq: 466 a.a.

Struc: 142 a.a.*

Protein chain

P08709  (FA7_HUMAN) -  Coagulation factor VII

Seq: 466 a.a.

Struc: 254 a.a.

Protein chain

P13726  (TF_HUMAN) -  Tissue factor

Seq: 295 a.a.

Struc: 191 a.a.

* 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.
• Reaction: Hydrolyzes one Arg-|-Ile bond in factor X to form factor Xa.

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (2 terms)
• Biological process: blood coagulation (2 terms)
• Biochemical function: catalytic activity (4 terms)

DOI no: 10.1016/j.bbrc.2004.12.042

Biochem Biophys Res Commun 327:589-596 (2005)

PubMed id: 15629154

Structure-based design of P3 moieties in the peptide mimetic factor VIIa inhibitor.

S.Kadono, A.Sakamoto, Y.Kikuchi, M.Oh-eda, N.Yabuta, K.Yoshihashi, T.Kitazawa, T.Suzuki, T.Koga, K.Hattori, T.Shiraishi, M.Haramura, H.Kodama, Y.Ono, T.Esaki, H.Sato, Y.Watanabe, S.Itoh, M.Ohta, T.Kozono.

ABSTRACT

Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is seen as a promising target for developing new anticoagulant drugs. Structure-based designs of the P3 moiety in the peptide mimetic factor VIIa inhibitor successfully lead to novel inhibitors with selectivity for FVIIa/TF and extrinsic coagulation the same as or even higher than those of previously reported peptide mimetic factor VIIa inhibitors. X-ray crystal structure analysis reveals that one of the novel inhibitors shows improved selectivity by forming interactions between the inhibitor and FVIIa as expected. Another of the novel inhibitors achieves improved selectivity through an unexpected hydrogen bond with Gln217, with a unique bent conformation in FVIIa/TF accompanied by conformational changes of the inhibitor and the protein.