5TQE

Factor VIIa in complex with the inhibitor (5R)-5-[(1-aminoisoquinolin-6-yl)amino]-19-(cyclopropylsulfonyl)-3-methyl-13-oxa-3,15-diazatricyclo[14.3.1.1~6,10~]henicosa-1(20),6(21),7,9,16,18-hexaene-4,14-dione

PDB DOI: https://doi.org/10.2210/pdb5TQE/pdb

Classification: HYDROLASE/HYDROLASE INHIBITOR
Organism(s): Homo sapiens
Expression System: Cricetinae
Mutation(s): No

Deposited: 2016-10-24 Released: 2017-02-01
Deposition Author(s): Wei, A.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.90 Å
R-Value Free: 0.209
R-Value Work: 0.184
R-Value Observed: 0.184

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.1 of the entry. See complete history.

Literature

Design and Synthesis of Novel Meta-Linked Phenylglycine Macrocyclic FVIIa Inhibitors.

Richter, J.M., Cheney, D.L., Bates, J.A., Wei, A., Luettgen, J.M., Rendina, A.R., Harper, T.M., Narayanan, R., Wong, P.C., Seiffert, D., Wexler, R.R., Priestley, E.S.

(2017) ACS Med Chem Lett 8: 67-72

PubMed: 28105277 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1021/acsmedchemlett.6b00375
Primary Citation of Related Structures:
5TQE, 5TQF, 5TQG

PubMed Abstract:
Two novel series of meta-linked phenylglycine-based macrocyclic FVIIa inhibitors have been designed to improve the rodent metabolic stability and PK observed with the precursor para-linked phenylglycine macrocycles. Through iterative structure-based design and optimization, the TF/FVIIa K _i was improved to subnanomolar levels with good clotting activity, metabolic stability, and permeability.

Organizational Affiliation

Research & Development, Bristol-Myers Squibb , Hopewell, New Jersey 08534, United States.

Macromolecule Content

Total Structure Weight: 35.42 kDa
Atom Count: 2,834
Modelled Residue Count: 307
Deposited Residue Count: 309
Unique protein chains: 2

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Factor VIIa (Heavy Chain)	A [auth H]	254	Homo sapiens	Mutation(s): 0 Gene Names: F7 EC: 3.4.21.21
UniProt & NIH Common Fund Data Resources
Find proteins for P08709 (Homo sapiens) Explore P08709 Go to UniProtKB: P08709
PHAROS: P08709 GTEx: ENSG00000057593
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P08709
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
Factor VIIa (Light Chain)	B [auth L]	55	Homo sapiens	Mutation(s): 0 Gene Names: F7 EC: 3.4.21.21
UniProt & NIH Common Fund Data Resources
Find proteins for P08709 (Homo sapiens) Explore P08709 Go to UniProtKB: P08709
PHAROS: P08709 GTEx: ENSG00000057593
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P08709
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
7KQ Query on 7KQ Download Ideal Coordinates CCD File SDF format, chain C [auth H] MOL2 format, chain C [auth H]	C [auth H]	(5R)-5-[(1-aminoisoquinolin-6-yl)amino]-19-(cyclopropylsulfonyl)-3-methyl-13-oxa-3,15-diazatricyclo[14.3.1.1~6,10~]henicosa-1(20),6(21),7,9,16,18-hexaene-4,14-dione C₃₁ H₃₁ N₅ O₅ S UCRGDFCSSTYSRG-MUUNZHRXSA-N		Interactions Focus chain C [auth H] Interactions & Density Focus chain C [auth H]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain E [auth H] SDF format, chain F [auth H] SDF format, chain G [auth H] SDF format, chain H MOL2 format, chain E [auth H] MOL2 format, chain F [auth H] MOL2 format, chain G [auth H] MOL2 format, chain H	E [auth H], F [auth H], G [auth H], H	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain E [auth H] Focus chain F [auth H] Focus chain G [auth H] Focus chain H Interactions & Density Focus chain E [auth H] Focus chain F [auth H] Focus chain G [auth H] Focus chain H
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain I [auth H] SDF format, chain J [auth H] SDF format, chain K [auth H] MOL2 format, chain I [auth H] MOL2 format, chain J [auth H] MOL2 format, chain K [auth H]	I [auth H], J [auth H], K [auth H]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain I [auth H] Focus chain J [auth H] Focus chain K [auth H] Interactions & Density Focus chain I [auth H] Focus chain J [auth H] Focus chain K [auth H]
CA Query on CA Download Ideal Coordinates CCD File SDF format, chain D [auth H] MOL2 format, chain D [auth H]	D [auth H]	CALCIUM ION Ca BHPQYMZQTOCNFJ-UHFFFAOYSA-N		Interactions Focus chain D [auth H] Interactions & Density Focus chain D [auth H]