PDBsum entry 4jyu

Hydrolase/hydrolase inhibitor

PDB id: 4jyu

Contents

Protein chains

254 a.a.

55 a.a.

Ligands

1OK

SO4 ×4

GOL ×4

Metals

_CA

Waters ×374

PDB id:

4jyu

Name:

Hydrolase/hydrolase inhibitor

Title:

Structure of factor viia in complex with the inhibitor (2r)-2-[(1- aminoisoquinolin-6-yl)amino]-2-[3-ethoxy-4-(propan-2-yloxy)phenyl]-n- (phenylsulfonyl)ethanamide

Structure:

Factor vii light chain. Chain: h. Synonym: proconvertin, serum prothrombin conversion accelerator, spca, coagulation factor vii. Engineered: yes. Factor vii heavy chain. Chain: l. Synonym: proconvertin, serum prothrombin conversion accelerator, spca, coagulation factor vii.

Source:

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

Resolution:

1.80Å R-factor: 0.176 R-free: 0.192

Authors:

A.Wei,R.Anumula

Key ref:

P.W.Glunz et al. (2013). Nonbenzamidine acylsulfonamide tissue factor-factor VIIa inhibitors. Bioorg Med Chem Lett, 23, 5244-5248. PubMed id: 23845220 DOI: 10.1016/j.bmcl.2013.06.027

Date:

01-Apr-13 Release date: 24-Jul-13

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: 55 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.2013.06.027

Bioorg Med Chem Lett 23:5244-5248 (2013)

PubMed id: 23845220

Nonbenzamidine acylsulfonamide tissue factor-factor VIIa inhibitors.

P.W.Glunz, X.Zhang, Y.Zou, I.Delucca, A.H.Nirschl, X.Cheng, C.A.Weigelt, D.L.Cheney, A.Wei, R.Anumula, J.M.Luettgen, A.R.Rendina, M.Harpel, G.Luo, R.Knabb, P.C.Wong, R.R.Wexler, E.S.Priestley.

ABSTRACT

Aminoisoquinoline and isoquinoline groups have successfully replaced the more basic P1 benzamidine group of an acylsulfonamide factor VIIa inhibitor. Inhibitory activity was optimized by the identification of additional hydrophobic and hydrophilic P' binding interactions. The molecular details of these interactions were elucidated by X-ray crystallography and molecular modeling. We also show that decreasing the basicity of the P1 group results in improved oral bioavailability in this chemotype.