PDBsum entry 2c4f

Hydrolase

PDB id: 2c4f

Contents

Protein chains

254 a.a. *

139 a.a. *

75 a.a. *

116 a.a. *

Ligands

GIL

GLC

FUC

NAG

Metals

_CA ×5

Waters ×328

* Residue conservation analysis

PDB id:

2c4f

Name:

Hydrolase

Title:

Crystal structure of factor vii.Stf complexed with pd0297121

Structure:

Coagulation factor vii precursor. Chain: h. Fragment: factor vii heavy chain, residues 213-466. Synonym: factor vii, serum prothrombin conversion accelerator, spca, proconvertin, eptacog alfa. Engineered: yes. Coagulation factor vii precursor. Chain: l. Fragment: factor vii light chain, residues 61-202.

Source:

Synthetic: yes. Homo sapiens. Organism_taxid: 9606. Organism_taxid: 9606

Biol. unit:

Tetramer (from PDB file)

Resolution:

1.72Å R-factor: 0.229

Authors:

J.T.Kohrt,E.Zhang

Key ref:

J.T.Kohrt et al. (2006). The discovery of fluoropyridine-based inhibitors of the factor VIIa/TF complex--Part 2. Bioorg Med Chem Lett, 16, 1060-1064. PubMed id: 16289811 DOI: 10.1016/j.bmcl.2005.10.076

Date:

18-Oct-05 Release date: 18-Oct-06

Protein chain

P08709  (FA7_HUMAN) -  Coagulation factor VII from Homo sapiens

Seq: 466 a.a.

Struc: 254 a.a.

Protein chain

P08709  (FA7_HUMAN) -  Coagulation factor VII from Homo sapiens

Seq: 466 a.a.

Struc: 139 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 H, L: E.C.3.4.21.21 - coagulation factor VIIa.
• Reaction: Hydrolyzes one Arg-|-Ile bond in factor X to form factor Xa.

DOI no: 10.1016/j.bmcl.2005.10.076

Bioorg Med Chem Lett 16:1060-1064 (2006)

PubMed id: 16289811

The discovery of fluoropyridine-based inhibitors of the factor VIIa/TF complex--Part 2.

J.T.Kohrt, K.J.Filipski, W.L.Cody, C.Cai, D.A.Dudley, C.A.Van Huis, J.A.Willardsen, L.S.Narasimhan, E.Zhang, S.T.Rapundalo, K.Saiya-Cork, R.J.Leadley, J.J.Edmunds.

ABSTRACT

The activated factor VII/tissue factor complex (FVIIa/TF) is known to play a key role in the formation of blood clots. Inhibition of this complex may lead to new antithrombotic drugs. A fluoropyridine-based series of FVIIa/TF inhibitors was discovered which utilized a diisopropylamino group for binding in the S2 and S3 binding pockets of the active site of the enzyme complex. In this series, an enhancement in binding affinity was observed by substitution at the 5-position of the hydroxybenzoic acid sidechain. An X-ray crystal structure indicates that amides at this position may increase inhibitor binding affinity through interactions with the S1'/S2' pocket.