3UH2

Tankyrase-1 in complexed with PJ34

PDB DOI: https://doi.org/10.2210/pdb3UH2/pdb

Classification: TRANSFERASE/TRANSFERASE INHIBITOR
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): Yes

Deposited: 2011-11-03 Released: 2012-02-15
Deposition Author(s): Kirby, C.A., Stams, T.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.00 Å
R-Value Free: 0.217
R-Value Work: 0.175
R-Value Observed: 0.177

Starting Model: experimental
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Ligand Structure Quality Assessment

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

Literature

Structure of human tankyrase 1 in complex with small-molecule inhibitors PJ34 and XAV939.

Kirby, C.A., Cheung, A., Fazal, A., Shultz, M.D., Stams, T.

(2012) Acta Crystallogr Sect F Struct Biol Cryst Commun 68: 115-118

PubMed: 22297980 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1107/S1744309111051219
Primary Citation of Related Structures:
3UH2, 3UH4

PubMed Abstract:
The crystal structures of tankyrase 1 (TNKS1) in complex with two small-molecule inhibitors, PJ34 and XAV939, both at 2.0 Å resolution, are reported. The structure of TNKS1 in complex with PJ34 reveals two molecules of PJ34 bound in the NAD(+) donor pocket. One molecule is in the nicotinamide portion of the pocket, as previously observed in other PARP structures, while the second molecule is bound in the adenosine portion of the pocket. Additionally, unlike the unliganded crystallization system, the TNKS1-PJ34 crystallization system has the NAD(+) donor site accessible to bulk solvent in the crystal, which allows displacement soaking. The TNKS1-PJ34 crystallization system was used to determine the structure of TNKS1 in complex with XAV939. These structures provide a basis for the start of a structure-based drug-design campaign for TNKS1.

Organizational Affiliation

Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA.

Macromolecule Content

Total Structure Weight: 52.61 kDa
Atom Count: 3,583
Modelled Residue Count: 407
Deposited Residue Count: 448
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Tankyrase-1	A, B	224	Homo sapiens	Mutation(s): 1 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 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
P34 Query on P34 Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain K [auth B] SDF format, chain L [auth B] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain K [auth B] MOL2 format, chain L [auth B] mmCIF format, chain D [auth A] mmCIF format, chain E [auth A] mmCIF format, chain K [auth B] mmCIF format, chain L [auth B]	D [auth A], E [auth A], K [auth B], L [auth B]	N~2~,N~2~-DIMETHYL-N~1~-(6-OXO-5,6-DIHYDROPHENANTHRIDIN-2-YL)GLYCINAMIDE C₁₇ H₁₇ N₃ O₂ UYJZZVDLGDDTCL-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain E [auth A] Focus chain K [auth B] Focus chain L [auth B] Interactions & Density Focus chain D [auth A] Focus chain E [auth A] Focus chain K [auth B] Focus chain L [auth B]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain I [auth A] SDF format, chain M [auth B] MOL2 format, chain F [auth A] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain I [auth A] MOL2 format, chain M [auth B] mmCIF format, chain F [auth A] mmCIF format, chain G [auth A] mmCIF format, chain H [auth A] mmCIF format, chain I [auth A] mmCIF format, chain M [auth B]	F [auth A], G [auth A], H [auth A], I [auth A], M [auth B]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain M [auth B] Interactions & Density Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain M [auth B]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain J [auth B] MOL2 format, chain C [auth A] MOL2 format, chain J [auth B] mmCIF format, chain C [auth A] mmCIF format, chain J [auth B]	C [auth A], J [auth B]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain J [auth B] Interactions & Density Focus chain C [auth A] Focus chain J [auth B]

Binding Affinity Annotations
ID	Source	Binding Affinity
P34	BindingDB: 3UH2	IC50: min: 39, max: 2951 (nM) from 6 assay(s)
P34	PDBBind: 3UH2	IC50: 1000 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.00 Å
R-Value Free: 0.217
R-Value Work: 0.175
R-Value Observed: 0.177
Space Group: C 1 2 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 125.26	α = 90
b = 43.3	β = 91.36
c = 88.54	γ = 90

Software Package:

Software Name	Purpose
ADSC	data collection
PHASER	phasing
BUSTER	refinement
autoPROC	data scaling
SCALA	data scaling

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2012-02-15

Deposition Author(s):

Kirby, C.A.

Stams, T.

Revision History (Full details and data files)

Version 1.0: 2012-02-15
Type: Initial release
Version 1.1: 2023-09-13
Changes: Data collection, Database references, Derived calculations, Refinement description