PDBsum entry: 1wtg

Hydrolase/blood clotting

PDB-id: 1wtg

Biological unit* = asymmetric unit, as shown
(*as deduced by PQS)

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Description

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Header records

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Protein chains

142 a.a. *

254 a.a. *

191 a.a. *

Ligands

BGC

FUC

3BP

Metal ions

_CA ×9

Waters ×511

* Residue conservation analysis

Tools

Clefts Calculation

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PDB id:

1wtg

Name:

Hydrolase/blood clotting

Title:

Human factor viia-tissue factor complexed with ethylsulfonamide-d-biphenylalanine-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.

Biological unit:

Trimer (from PQS)

UniProt:

Chain L: P08709 (FA7_HUMAN)

Seq:
Struc:
	Seq:	466 a.a.
	Struc:	142 a.a.*

Chain H: P08709 (FA7_HUMAN)

Seq:
Struc:
	Seq:	466 a.a.
	Struc:	254 a.a.

Chain T: P13726 (TF_HUMAN)

Seq:

Struc:

Seq:

295 a.a.

Struc:

191 a.a.

Key:	PfamA domain
Secondary structure	CATH domain

* PDB and UniProt seqs differ at 10 residue positions (black crosses)

Enzyme class:

Chains L, H: E.C.3.4.21.21   [IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Reaction:

Hydrolyzes one Arg-|-Ile bond in factor X to form factor Xa.

Resolution:

2.20Å

R-factor:

0.204

R-free:

0.251

Authors:

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

Key ref:

S.Kadono et al. (2005). Novel interactions of large P3 moiety and small P4 moiety in the binding of the peptide mimetic factor VIIa inhibitor.. Biochem Biophys Res Commun, 326, 859-865. [PubMed id: 15607748] [DOI: 10.1016/j.bbrc.2004.11.108]

Date:

23-Nov-04

Release date:

23-Nov-05

Related entries:

1wss
the same protein complexed with another inhibitor
1wqv
the same protein complexed with another inhibitor
1dan
the same protein complexed with irreversible inhibitor

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Surface

Key reference

DOI no: 10.1016/j.bbrc.2004.11.108

Biochem Biophys Res Commun 326:859-865 (2005)

PubMed id: 15607748

Novel interactions of large P3 moiety and small P4 moiety in the binding of 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. A novel peptide mimetic factor VIIa inhibitor, ethylsulfonamide-d-biphenylalanine-Gln-p-aminobenzamidine, shows 100-fold selectivity against thrombin in spite of its large P3 moiety, unlike previously reported FVIIa/TF selective inhibitors. X-ray crystal structure analysis reveals that the large P3 moiety, d-biphenylalanine, and the small P4 moiety, ethylsulfonamide, make novel interactions with the 170-loop and Lys192 of FVIIa/TF, respectively, accompanying ligand-induced conformational changes of the 170-loop, Gln217, and Lys192. Structural comparisons of FVIIa with thrombin and amino acid sequence comparisons among coagulation serine proteases suggest that these interactions play an important role in achieving selective inhibition for FVIIa/TF.