3KJD

Human poly(ADP-ribose) polymerase 2, catalytic fragment in complex with an inhibitor ABT-888

PDB DOI: https://doi.org/10.2210/pdb3KJD/pdb

Deposited: 2009-11-03 Released: 2009-11-17
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., Roos, A.K., 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: 1.95 Å
R-Value Free: 0.232
R-Value Work: 0.179
R-Value Observed: 0.182

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Crystal structure of the catalytic domain of human PARP2 in complex with PARP inhibitor ABT-888.

Karlberg, T., Hammarstrom, M., Schutz, P., Svensson, L., Schuler, H.

(2010) Biochemistry 49: 1056-1058

PubMed: 20092359 Search on PubMed
DOI: https://doi.org/10.1021/bi902079y
Primary Citation of Related Structures:
3KCZ, 3KJD

PubMed Abstract:
Poly-ADP-ribose polymerases (PARPs) catalyze transfer of ADP-ribose from NAD(+) to specific residues in their substrate proteins or to growing ADP-ribose chains. PARP activity is involved in processes such as chromatin remodeling, transcription control, and DNA repair. Inhibitors of PARP activity may be useful in cancer therapy. PARP2 is the family member that is most similar to PARP1, and the two can act together as heterodimers. We used X-ray crystallography to determine two structures of the catalytic domain of human PARP2: the complexes with PARP inhibitors 3-aminobenzamide and ABT-888. These results contribute to our understanding of structural features and compound properties that can be employed to develop selective inhibitors of human ADP-ribosyltransferases.

Organizational Affiliation

Structural Genomics Consortium, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles vag 2, 17177 Stockholm, Sweden.

Macromolecule Content

Total Structure Weight: 84.33 kDa
Atom Count: 6,105
Modelled Residue Count: 702
Deposited Residue Count: 736
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Poly [ADP-ribose] polymerase 2	A, B	368	Homo sapiens	Mutation(s): 0 Gene Names: ADPRT2, ADPRTL2, PARP2 EC: 2.4.2.30
UniProt & NIH Common Fund Data Resources
Find proteins for Q9UGN5 (Homo sapiens) Explore Q9UGN5 Go to UniProtKB: Q9UGN5
PHAROS: Q9UGN5 GTEx: ENSG00000129484
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q9UGN5
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
78P Query on 78P Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain E [auth B] MOL2 format, chain C [auth A] MOL2 format, chain E [auth B]	C [auth A], E [auth B]	(2R)-2-(7-carbamoyl-1H-benzimidazol-2-yl)-2-methylpyrrolidinium C₁₃ H₁₆ N₄ O JNAHVYVRKWKWKQ-CYBMUJFWSA-N		Interactions Focus chain C [auth A] Focus chain E [auth B] Interactions & Density Focus chain C [auth A] Focus chain E [auth B]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain F [auth B] MOL2 format, chain D [auth A] MOL2 format, chain F [auth B]	D [auth A], F [auth B]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain F [auth B] Interactions & Density Focus chain D [auth A] Focus chain F [auth B]

Binding Affinity Annotations
ID	Source	Binding Affinity
78P	BindingDB: 3KJD	Kd: 5.8 (nM) from 1 assay(s)
	BindingDB: 3KJD	IC50: min: 1.3, max: 138 (nM) from 8 assay(s)
	Binding MOAD: 3KJD	Kd: 2.9 (nM) from 1 assay(s)
	PDBBind: 3KJD	Kd: 2.9 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.95 Å
R-Value Free: 0.232
R-Value Work: 0.179
R-Value Observed: 0.182
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 58.134	α = 90
b = 134.611	β = 117.68
c = 58.314	γ = 90

Software Package:

Software Name	Purpose
DNA	data collection
MOLREP	phasing
REFMAC	refinement
XDS	data reduction
XSCALE	data scaling

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2009-11-17

Deposition Author(s):

Structural Genomics Consortium (SGC)

Revision History (Full details and data files)

Version 1.0: 2009-11-17
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, Structure summary