4U6A

X-ray crystal structure of human TNKS in complex with a small molecule inhibitor

PDB DOI: https://doi.org/10.2210/pdb4U6A/pdb

Classification: TRANSFERASE
Organism(s): Homo sapiens
Expression System: Escherichia coli BL21(DE3)
Mutation(s): Yes

Deposited: 2014-07-28 Released: 2015-07-08
Deposition Author(s): Oliver, A.W.
Funding Organization(s): Wellcome Trust

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.37 Å
R-Value Free: 0.248
R-Value Work: 0.191
R-Value Observed: 0.194

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.2 of the entry. See complete history.

Literature

Design and discovery of 3-aryl-5-substituted-isoquinolin-1- ones as potent and selective tankyrase inhibitors

Elliot, R.J., Jarvis, A., Rajasekaran, M.B., Menon, M., Bowers, L., Boffey, R., Bayford, M., Firth-Clark, S., Beevers, R., Aquil, R., Kirton, S.B., Niculescu-Duvaz, D., Fish, L., Lopes, F., McLeary, R., Trindade, I., Vendrell, E., Munkonge, F., Porter, R., Perrior, T., Springer, C., Oliver, A.W., Pearl, L.H., Ashworth, A., Lord, C.J.

To be published.

Macromolecule Content

Total Structure Weight: 30.44 kDa
Atom Count: 1,806
Modelled Residue Count: 205
Deposited Residue Count: 258
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Tankyrase-1	A	258	Homo sapiens	Mutation(s): 1 Gene Names: TNKS, PARP5A, PARPL, TIN1, TINF1, TNKS1 EC: 2.4.2.30 (PDB Primary Data), 2.4.2 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for O95271 (Homo sapiens) Explore O95271 Go to UniProtKB: O95271
PHAROS: O95271 GTEx: ENSG00000173273
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	O95271
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
3DN Query on 3DN Download Ideal Coordinates CCD File SDF format, chain C [auth A] MOL2 format, chain C [auth A] mmCIF format, chain C [auth A]	C [auth A]	3-(4-{[4-(dimethylamino)piperidin-1-yl]methyl}phenyl)-5-methylisoquinolin-1(2H)-one C₂₄ H₂₉ N₃ O ZAVBKFISCRSHAT-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain F [auth A] SDF format, chain H [auth A] SDF format, chain J [auth A] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] MOL2 format, chain H [auth A] MOL2 format, chain J [auth A] mmCIF format, chain D [auth A] mmCIF format, chain E [auth A] mmCIF format, chain F [auth A] mmCIF format, chain H [auth A] mmCIF format, chain J [auth A]	D [auth A], E [auth A], F [auth A], H [auth A], J [auth A]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain H [auth A] Focus chain J [auth A] Interactions & Density Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain H [auth A] Focus chain J [auth A]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A] mmCIF format, chain B [auth A]	B [auth A]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain I [auth A] MOL2 format, chain G [auth A] MOL2 format, chain I [auth A] mmCIF format, chain G [auth A] mmCIF format, chain I [auth A]	G [auth A], I [auth A]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain G [auth A] Focus chain I [auth A] Interactions & Density Focus chain G [auth A] Focus chain I [auth A]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.37 Å
R-Value Free: 0.248
R-Value Work: 0.191
R-Value Observed: 0.194
Space Group: I 2₁ 2₁ 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 81.38	α = 90
b = 80.98	β = 90
c = 84.02	γ = 90

Software Package:

Software Name	Purpose
BUSTER	refinement
XDS	data reduction
Aimless	data scaling
PDB_EXTRACT	data extraction
PHASER	phasing
XSCALE	data reduction
XSCALE	data scaling

Structure Validation

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Ligand Structure Quality Assessment

Entry History & Funding Information

Deposition Data

Released Date: 2015-07-08

Deposition Author(s):

Oliver, A.W.

Funding Organization	Location	Grant Number
Wellcome Trust	United Kingdom	SDDI

Revision History (Full details and data files)

Version 1.0: 2015-07-08
Type: Initial release
Version 1.1: 2015-07-15
Changes: Other
Version 1.2: 2023-12-20
Changes: Data collection, Database references, Derived calculations, Refinement description

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Help and Resources

4U6A

X-ray crystal structure of human TNKS in complex with a small molecule inhibitor

Design and discovery of 3-aryl-5-substituted-isoquinolin-1- ones as potent and selective tankyrase inhibitors

Entity ID: 1

UniProt & NIH Common Fund Data Resources

Entity Groups

Sequence Annotations

Expand

Experimental Data

Structure Validation

Ligand Structure Quality Assessment

Deposition Data

Revision History (Full details and data files)