2UWP

Factor Xa inhibitor complex

PDB DOI: https://doi.org/10.2210/pdb2UWP/pdb

Classification: HYDROLASE
Organism(s): Homo sapiens
Mutation(s): No

Deposited: 2007-03-22 Released: 2007-05-08
Deposition Author(s): Young, R.J., Brown, D., Burns-Kurtis, C.L., Chan, C., Convery, M.A., Hubbard, J.A., Kelly, H.A., Pateman, A.J., Patikis, A., Senger, S., Shah, G.P., Toomey, J.R., Watson, N.S., Zhou, P., Thorpe, J.H.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.75 Å
R-Value Free: 0.212
R-Value Work: 0.185
R-Value Observed: 0.186

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Literature

Selective and Dual Action Orally Active Inhibitors of Thrombin and Factor Xa.

Young, R.J., Brown, D., Burns-Kurtis, C.L., Chan, C., Convery, M.A., Hubbard, J.A., Kelly, H.A., Pateman, A.J., Patikis, A., Senger, S., Shah, G.P., Toomey, J.R., Watson, N.S., Zhou, P.

(2007) Bioorg Med Chem Lett 17: 2927

PubMed: 17420122 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2007.03.080
Primary Citation of Related Structures:
2UWL, 2UWO, 2UWP

PubMed Abstract:
The synthetic entry to new classes of dual fXa/thrombin and selective thrombin inhibitors with significant oral bioavailability is described. This was achieved through minor modifications to the sulfonamide group in our potent and selective fXa inhibitor (E)-2-(5-chlorothien-2-yl)-N-{(3S)-1-[(1S)-1-methyl-2-(morpholin-4-yl)-2-oxoethyl]-2-oxopyrrolidin-3-yl}ethenesulfonamide and these observed activity changes have been rationalised using structural studies.

Organizational Affiliation

GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK. Rob.J.Young@gsk.com

Macromolecule Content

Total Structure Weight: 44.28 kDa
Atom Count: 2,507
Modelled Residue Count: 287
Deposited Residue Count: 388
Unique protein chains: 2

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
COAGULATION FACTOR X	A	254	Homo sapiens	Mutation(s): 0 EC: 3.4.21.6
UniProt & NIH Common Fund Data Resources
Find proteins for P00742 (Homo sapiens) Explore P00742 Go to UniProtKB: P00742
PHAROS: P00742 GTEx: ENSG00000126218
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P00742
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
COAGULATION FACTOR X	B	134	Homo sapiens	Mutation(s): 0 EC: 3.4.21.6
UniProt & NIH Common Fund Data Resources
Find proteins for P00742 (Homo sapiens) Explore P00742 Go to UniProtKB: P00742
PHAROS: P00742 GTEx: ENSG00000126218
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P00742
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
894 Query on 894 Download Ideal Coordinates CCD File SDF format, chain C [auth A] MOL2 format, chain C [auth A]	C [auth A]	2-(5-CHLORO-2-THIENYL)-N-{(3S)-1-[(1S)-1-METHYL-2-MORPHOLIN-4-YL-2-OXOETHYL]-2-OXOPYRROLIDIN-3-YL}ETHANESULFONAMIDE C₁₇ H₂₄ Cl N₃ O₅ S₂ IAUZEBLXCOCAFL-JSGCOSHPSA-N		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]
CA Query on CA Download Ideal Coordinates CCD File SDF format, chain D [auth A] MOL2 format, chain D [auth A]	D [auth A]	CALCIUM ION Ca BHPQYMZQTOCNFJ-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Interactions & Density Focus chain D [auth A]
MG Query on MG Download Ideal Coordinates CCD File SDF format, chain E [auth A] MOL2 format, chain E [auth A]	E [auth A]	MAGNESIUM ION Mg JLVVSXFLKOJNIY-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Interactions & Density Focus chain E [auth A]

Binding Affinity Annotations
ID	Source	Binding Affinity
894	Binding MOAD: 2UWP	Ki: 154 (nM) from 1 assay(s)
	BindingDB: 2UWP	Ki: 154 (nM) from 1 assay(s)
	PDBBind: 2UWP	Ki: 154 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.75 Å
R-Value Free: 0.212
R-Value Work: 0.185
R-Value Observed: 0.186
Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 56.448	α = 90
b = 71.963	β = 90
c = 78.671	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
MOSFLM	data reduction
SCALA	data scaling

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2007-05-08

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2007-05-08
Type: Initial release
Version 1.1: 2011-05-08
Changes: Version format compliance
Version 1.2: 2011-07-13
Changes: Version format compliance
Version 1.3: 2023-12-13
Changes: Data collection, Database references, Derived calculations, Other, Refinement description