PDBsum entry: 2c4f

Hydrolase

PDB-id: 2c4f

Biological unit = asymmetric unit, as shown
(as defined in PDB file)

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Description

Header details

Header records

References

PROCHECK

Protein chains

254 a.a. *

139 a.a. *

75 a.a. *

116 a.a. *

Ligands

GIL

GLC

FUC

NAG

Metal ions

_CA ×5

Waters ×328

* Residue conservation analysis

Tools

Clefts Calculation

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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. Coagulation factor vii precursor. Chain: l. Fragment: factor vii light chain, residues 61-202. Synonym: factor vii, serum prothrombin conversion

Source:

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

Biological unit:

Tetramer (from PDB file)

UniProt:

Chain H: P08709 (FA7_HUMAN)

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

Chain L: P08709 (FA7_HUMAN)

Seq:
Struc:
	Seq:	466 a.a.
	Struc:	139 a.a.*

Chain T: P13726 (TF_HUMAN)

Seq:
Struc:
	Seq:	295 a.a.
	Struc:	75 a.a.

Chain U: P13726 (TF_HUMAN)

Seq:

Struc:

Seq:

295 a.a.

Struc:

116 a.a.

Key:	PfamA domain
Secondary structure	CATH domain

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

Enzyme class:

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

Reaction:

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

Resolution:

1.72Å

R-factor:

0.228

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

Related entries:

1ahw a complex of extracellular domain of tissue factor with an inhibitory fab (5g9)
1boy extracellular region of human tissue factor
1bf9 n-terminal egf-like domain from human factor vii, nmr, 23 structures
1tfh extracellular domain of human tissue factor
1uj3 crystal structure of a humanized fab fragment of anti-tissue-factor antibody in complex with tissue factor
2hft mol_id: 1; molecule: human tissue factor; chain: null; domain: extracellular domain, residues 1 - 219; engineered: yes
1cvw crystal structure of active site-inhibited human coagulation factor viia (des-gla)
1dan complex of active site inhibited human blood coagulation factor viia with human recombinant soluble tissue factor
1dva crystal structure of the complex between the peptide exosite inhibitor e-76 and coagulation factor viia
1f7e the first egf-like domain from human blood coagulation fvii, nmr, 20 structures
... plus others (see Header records)

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Key reference

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.