PDBsum entry 2ec9

Blood clotting

PDB id: 2ec9

Contents

Protein chains

142 a.a. *

254 a.a. *

75 a.a. *

116 a.a. *

Ligands

ASO

FUC

24X

Metals

_CA ×9

Waters ×224

* Residue conservation analysis

PDB id:

2ec9

Name:

Blood clotting

Title:

Crystal structure analysis of human factor viia , souluble tissue factor complexed with bcx-3607

Structure:

Coagulation factor vii. Chain: l. Fragment: residues 1-142. Synonym: serum prothrombin conversion accelerator, spca, proconvertin, eptacog alfa. Engineered: yes. Coagulation factor vii. Chain: h. Fragment: residues 16-257.

Source:

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

Resolution:

2.00Å R-factor: 0.242 R-free: 0.282

Authors:

K.Raman,B.Yarlagadda

Key ref:

R.Krishnan et al. (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. PubMed id: 17505107

Date:

13-Feb-07 Release date: 19-Feb-08

Protein chain

P08709  (FA7_HUMAN) -  Coagulation factor VII from Homo sapiens

Seq: 466 a.a.

Struc: 142 a.a.*

Protein chain

P08709  (FA7_HUMAN) -  Coagulation factor VII from Homo sapiens

Seq: 466 a.a.

Struc: 254 a.a.

Protein chain

P13726  (TF_HUMAN) -  Tissue factor from Homo sapiens

Seq: 295 a.a.

Struc: 75 a.a.

Protein chain

P13726  (TF_HUMAN) -  Tissue factor from Homo sapiens

Seq: 295 a.a.

Struc: 116 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.

Acta Crystallogr D Biol Crystallogr 63:689-697 (2007)

PubMed id: 17505107

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.

R.Krishnan, P.L.Kotian, P.Chand, S.Bantia, S.Rowland, Y.S.Babu.

ABSTRACT

Factor VIIa (FVIIa) is a trypsin-like serine protease in the coagulation cascade. Its complex with tissue factor (TF) triggers the extrinsic pathway of the coagulation cascade, generating a blood clot. Research programs at several centers now recognize the important roles played by TF and FVIIa in both the thrombotic and inflammatory processes associated with cardiovascular diseases. Therefore, inhibition of the TF-FVIIa complex is seen as a promising target that is key to the development of clinical candidates for various cardiovascular applications. The crystal structure of the TF-FVIIa enzyme complex has been analyzed in order to design and synthesize small-molecule inhibitors. Using structure-based drug design (SBDD), a new series of inhibitors have been discovered that demonstrate high potency against the TF-FVIIa complex while maintaining substantial selectivity versus other closely related serine proteases such as trypsin, thrombin, factor Xa and plasmin.