3KR8

Human tankyrase 2 - catalytic PARP domain in complex with an inhibitor XAV939

PDB DOI: https://doi.org/10.2210/pdb3KR8/pdb

Deposited: 2009-11-18 Released: 2009-12-15
Deposition Author(s): Karlberg, T., Schutz, P., Arrowsmith, C.H., Berglund, H., Bountra, C., Collins, R., Edwards, A.M., Flodin, S., Flores, A., Graslund, S., Hammarstrom, M., Johansson, A., Johansson, I., Kallas, A., Kotenyova, T., Kotzsch, A., Kraulis, P., Nielsen, T.K., Moche, M., Nordlund, P., Nyman, T., Persson, C., Siponen, M.I., Thorsell, A.G., Tresaugues, L., Van Den Berg, S., Weigelt, J., Welin, M., Wisniewska, M., Schuler, H., Structural Genomics Consortium (SGC)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.10 Å
R-Value Free: 0.255
R-Value Work: 0.198
R-Value Observed: 0.201

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Structural basis for the interaction between tankyrase-2 and a potent Wnt-signaling inhibitor.

Karlberg, T., Markova, N., Johansson, I., Hammarstrom, M., Schutz, P., Weigelt, J., Schuler, H.

(2010) J Med Chem 53: 5352-5355

PubMed: 20565110 Search on PubMed
DOI: https://doi.org/10.1021/jm100249w
Primary Citation of Related Structures:
3KR7, 3KR8

PubMed Abstract:
We report two crystal structures of the PARP domain of human tankyrase-2 (TNKS2). Tankyrases are involved in fundamental cellular processes such as telomere homeostasis and Wnt signaling. The complex of TNKS2 with the potent inhibitor XAV939 provides insights into the molecular basis of the strong interaction and suggests routes for further development of tankyrase inhibitors.

Organizational Affiliation

Structural Genomics Consortium, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-17177 Stockholm, Sweden.

Macromolecule Content

Total Structure Weight: 55.92 kDa
Atom Count: 3,767
Modelled Residue Count: 414
Deposited Residue Count: 480
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-2	A, B [auth C]	240	Homo sapiens	Mutation(s): 0 Gene Names: PARP5B, TANK2, TNKL, TNKS2 EC: 2.4.2.30
UniProt & NIH Common Fund Data Resources
Find proteins for Q9H2K2 (Homo sapiens) Explore Q9H2K2 Go to UniProtKB: Q9H2K2
PHAROS: Q9H2K2 GTEx: ENSG00000107854
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q9H2K2
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
XAV Query on XAV Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain I [auth C] MOL2 format, chain D [auth A] MOL2 format, chain I [auth C]	D [auth A], I [auth C]	2-[4-(trifluoromethyl)phenyl]-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidin-4-ol C₁₄ H₁₁ F₃ N₂ O S KLGQSVMIPOVQAX-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain I [auth C] Interactions & Density Focus chain D [auth A] Focus chain I [auth C]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain F [auth A] SDF format, chain J [auth C] SDF format, chain K [auth C] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] MOL2 format, chain J [auth C] MOL2 format, chain K [auth C]	E [auth A], F [auth A], J [auth C], K [auth C]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain E [auth A] Focus chain F [auth A] Focus chain J [auth C] Focus chain K [auth C] Interactions & Density Focus chain E [auth A] Focus chain F [auth A] Focus chain J [auth C] Focus chain K [auth C]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain L [auth C] SDF format, chain G [auth A] MOL2 format, chain L [auth C] MOL2 format, chain G [auth A]	G [auth A], L [auth C]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain G [auth A] Focus chain L [auth C] Interactions & Density Focus chain G [auth A] Focus chain L [auth C]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain H [auth C] MOL2 format, chain C [auth A] MOL2 format, chain H [auth C]	C [auth A], H [auth C]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain H [auth C] Interactions & Density Focus chain C [auth A] Focus chain H [auth C]

Binding Affinity Annotations
ID	Source	Binding Affinity
XAV	BindingDB: 3KR8	Kd: min: 4.2, max: 14 (nM) from 3 assay(s)
	BindingDB: 3KR8	IC50: min: 2.1, max: 17 (nM) from 9 assay(s)
	Binding MOAD: 3KR8	Kd: 8 (nM) from 1 assay(s)
	PDBBind: 3KR8	Kd: 8 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.10 Å
R-Value Free: 0.255
R-Value Work: 0.198
R-Value Observed: 0.201
Space Group: C 2 2 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 90.75	α = 90
b = 97.975	β = 90
c = 119.464	γ = 90

Software Package:

Software Name	Purpose
PROTEUM PLUS	data collection
MOLREP	phasing
REFMAC	refinement
SAINT	data reduction
SAINT	data scaling

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2009-12-15

Deposition Author(s):

Structural Genomics Consortium (SGC)

Revision History (Full details and data files)

Version 1.0: 2009-12-15
Type: Initial release
Version 1.1: 2011-07-13
Changes: Non-polymer description, Version format compliance
Version 1.2: 2023-11-01
Changes: Data collection, Database references, Derived calculations, Refinement description

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Help and Resources

3KR8

Human tankyrase 2 - catalytic PARP domain in complex with an inhibitor XAV939

Structural basis for the interaction between tankyrase-2 and a potent Wnt-signaling inhibitor.

Entity ID: 1

UniProt & NIH Common Fund Data Resources

Entity Groups

Sequence Annotations

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Experimental Data

Structure Validation

Ligand Structure Quality Assessment

Deposition Data

Revision History (Full details and data files)