PDBsum entry 4yt7

Hydrolase/hydrolase inhibitor

PDB id: 4yt7

Contents

Protein chains

254 a.a.

57 a.a.

Ligands

4K1

SO4 ×4

GOL ×2

Metals

_CA

Waters ×248

PDB id:

4yt7

Name:

Hydrolase/hydrolase inhibitor

Title:

Factor viia in complex with the inhibitor 2-(2-{(r)-[(4- carbamimidoylphenyl)amino][5-ethoxy-2-fluoro-3-(propan-2-yloxy) phenyl]methyl}-1h-imidazol-4-yl)benzamide

Structure:

Coagulation factor vii (heavy chain). Chain: h. Fragment: unp residues 213-466. Synonym: factor viia heavy chain, activated factor viia heavy chain, proconvertin, serum prothrombin conversion accelerator, spca. Engineered: yes. Coagulation factor vii (light chain). Chain: l. Fragment: unp residues 148-204.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: f7. Expressed in: cricetinae. Expression_system_taxid: 10026. Expression_system_taxid: 10026

Resolution:

2.30Å R-factor: 0.174 R-free: 0.198

Authors:

A.Wei

Key ref:

P.W.Glunz et al. (2015). Design and synthesis of potent, selective phenylimidazole-based FVIIa inhibitors. Bioorg Med Chem Lett, 25, 2169-2173. PubMed id: 25881820 DOI: 10.1016/j.bmcl.2015.03.062

Date:

17-Mar-15 Release date: 29-Apr-15

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: 57 a.a.

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.2015.03.062

Bioorg Med Chem Lett 25:2169-2173 (2015)

PubMed id: 25881820

Design and synthesis of potent, selective phenylimidazole-based FVIIa inhibitors.

P.W.Glunz, X.Cheng, D.L.Cheney, C.A.Weigelt, A.Wei, J.M.Luettgen, P.C.Wong, R.R.Wexler, E.S.Priestley.

ABSTRACT

Heterocyclic amide isosteres were incorporated into a phenylglycine-based tissue factor/factor VIIa (TF-FVIIa) inhibitor chemotype, providing potent inhibitors. An X-ray co-crystal structure of phenylimidazole 19 suggested that an imidazole nitrogen atom effectively mimics an amide carbonyl, while the phenyl ring forms key hydrophobic interactions with the S1' pocket. Exploration of phenylimidazole substitution led to the discovery of potent, selective and efficacious inhibitors of TF-FVIIa.