Crystal structures of ADP-ribosyl transferases

Human PARP1 (ARTD1)

Catalytic domain in complex with PARP inhibitors

Structures of PARP1 with PARPi

PARP inhibitors bound to PARP1. Structures were deposited in PDB (Rucaparib, 4RV6; Niraparib, 4R6E; XAV939, 4R5W; PJ34, 4UXB; Talazoparib, 4UND). Published in Thorsell et al. Journal of Medicinal Chemistry, 2017.

Human PARP2 (ARTD2)

Catalytic domain in complex with inhibitors 3-Aminobenzamide and Veliparib

Detailed view of the bound inhibitor Veliparib (ABT-888) to PARP2 in the NAD+ binding site. The SIGMAA-weighted Fobs- Fcalc electron density map for the ligand, rendered at 3.5 sigma, is shown. Crystal of PARP2 co-crystallized with Veliparib mounted on a loop is shown to the right. Structures deposited in PDB; PARP2 in complex with 3-Aminobenzamide (PDB: 3KCZ) and with ABT-888 (PDB: 3KJD). Published in Karlberg et al. Biochemistry, 2010.

Human PARP3 (ARTD3)

Catalytic domain in complex with PARP3-specific inhibitors

Structures of the catalytic domain of PARP3 in complex with PARP3-specific inhibitors (ME0328 and ME0355) were obtained. The figure shows the detailed interactions of ME0328 to the NAD+ binding site of PARP3. Structures deposited in PDB; PARP3 in complex with ME0328 (PDB: 4GV4), with ME0355 (PDB: 4GV0) and with its enantiomer ME0354 (PDB: 4GV2). Published in Lindgren et al. ACS Chemical Biology, 2013.

Catalytic domain in complex with PARP inhibitors

Structures of the catalytic domain of PARP3 in complex with four common PARP inhibitors (3-Aminobenzamide, DR-2313, PJ-34 and KU0058948) were obtained. The figure shows the detailed interactions of KU0058948 to the NAD+ binding site of PARP3. Structures deposited in PDB; PARP3 in complex with 3-Aminobenzamide (PDB: 3FHB), with KU0058948 (PDB: 3C49), with DR2313 (PDB: 3C4H) and with PJ34 (PDB: 3CE0). Published in Lehtiö et al. Journal of Medicinal Chemistry, 2009.

Human Tankyrase-1 (ARTD5)

Crystal structure of human Tankyrase-1 (ARTD5). The structure revealed that tankyrases contain a short zinc-binding motif, which was not predicted. The zinc ion is visualized as a purple sphere. Structure deposited in PDB; catalytic fragment of Tankyrase-1 (PDB: 2RF5). Published in Lehtiö et al. Journal of Molecular Biology, 2008.

Human Tankyrase-2 (ARTD6)

Catalytic domain in complex with inhibitor XAV939

Human Tankyrase-2 in complex with the potent inhibitor XAV939, PARP2 (in blue) superimposed onto the occupied ligand binding pocket, illustrating the positioning of α-helix-5 of the regulatory domain near the NAD+ cleft opening, and conserved side chains in the nicotinamide binding crevice. Structures deposited in PDB; Tankyrase-2 apo structure (PDB: 3KR7) and in complex with XAV939 (PDB: 3KR8). Published in Karlberg et al. Journal of Medicinal Chemistry, 2010.

Catalytic domain in complex with ligands from screening

Details of the active sites in Tankyrase-2 protein:ligand complexes. Electron densites of the ligands were contoured at 1.0 SIGMA in a 2Fobs-Fcalc map. Tankyrase-2 in complex with compounds (1) ENAMINE, T598968, (2) Maybridge, RF03877, (3) CHEMDIV, C800-1144, (4) CHEMDIV, F019-2529 and (5) CHEMDIV, 8233-1036. Structures deposited in PDB; (1) (PDB: 3MHJ), (2) (PDB: 3MHK), (3) (PDB: 3P0N), (4) (PDB: 3P0P) and (5) (PDB: 3P0Q). Published in Wahlberg et al. Nature Biotechnology, 2012.

Human PARP10 (ARTD10)

Catalytic domain in complex with inhibitor 3-Aminobenzamide

Human PARP10 (ARTD10) in complex with 3-aminobenzamide acid. Structure deposited in PDB; (PDB: 3HKV)

Human PARP12 (ARTD12)

Catalytic domain in complex with 3-Aminobenzoic acid

Human PARP12 (ARTD12) in complex with 3-aminobenzoic acid. Structure deposited in PDB; (PDB: 2PQF). Published in Karlberg et al. Journal of Biological Chemistry, 2015 (accepted).

Human PARP13 (ARTD13, ZC3HAV1, ZAP)

Crystal structure of human PARP13 (ARTD13). Structure deposited in PDB; (PDB: 2X5Y). Published in Karlberg et al. Journal of Biological Chemistry, 2015 (accepted).

Human PARP14 (ARTD8)

Catalytic domain in complex with PARP inhibitors

Structures of the catalytic domain of PARP14 (ARTD8) in complex with four PARP inhibitors 3-Aminobenzamide, 6(5H)-phenanthridinone, STO1190 (ENAMINE T5867921) and STO1262 (CHEMDIV, 3909-7439) were obtained. The figure shows details of PARP14:STO1190 interactions in the binding pocket. Electron densites of the ligands were contoured at 1.0 SIGMA in a 2Fobs-Fcalc map. The structures have been deposited in PDB; PARP14 in complex with 3-Aminobenzamide (PDB: 3GOY), with 6(5H)-phenanthridinone (PDB: 3SE2), with STO1190 (PDB: 3SMI) and with STO1262 (PDB: 3SMJ). Published in Wahlberg et al. Nature Biotechnology, 2012.

Catalytic domain in complex with ligands from virtual screening

The figure shows one isomer of the most promising hit compound A16(Z) from docking-based virtual screening bound to PARP14 (ARTD8) in a complex crystal structure. Electron densites of the ligands were contoured at 1.2 SIGMA in a 2Fobs-Fcalc map. Structures have been deposited in PDB; PARP14 in complex with A16(Z) (PDB: 4F1L) and with A16(E) (PDB: 4F1Q). Published in Andersson et al. Journal of Medicinal Chemistry, 2012.

Macro domains in complex with ADP-ribose

The figure shows the two-domain structure of PARP14 macrodomains 1 and 2 in complex with ADP-ribose (left). Electrostatic surface potential of PARP14 macro3 and ADP-ribose bound in a deep cleft is shown (right). Structures have been deposited in PDB; macro domains 1 and 2 in complex with ADP-ribose (PDB: 3VFQ), macro domains 1 and 2 in complex with ADP (PDB: 4D86), macro domain 1 in complex with ADP-ribose (PDB: 3Q6Z), macro domain 2 in complex with ADP-ribose (PDB: 3Q71), macro domain 3 in complex with ADP-ribose (PDB: 4ABK) and macro domain 3 without ligands (PDB: 4ABL). Published in Forst et al. Structure, 2013.

Human PARP15 (ARTD7)

Catalytic domain in complex with PJ34 and STO1102

Structures of the catalytic domain of PARP15 (ARTD7) in complex with PARP inhibitors PJ34 and STO1102 (ENAMINE, T5636531) were obtained. The figure shows STO1102 bound to PARP15, the D-loop is shown in gold. The structures have been deposited in PDB; PARP15 in complex with PJ34 (PDB: 3GEY), with STO1102 (PDB: 4F0E) and without any ligands (PDB: 3BLJ). Published in Andersson et al. Journal of Medicinal Chemistry, 2012.

Macro domain 2 in complex with ADP-ribose

The figure shows the structure of PARP15 (ARTD7) macrodomain 2 in complex with ADP-ribose. The structure has been deposited in PDB (PDB: 3V2B). Published in Forst et al. Structure, 2013.

Human PARP16 (ARTD15)

Crystal structure of human ARTD15/PARP16 reveals a novel putative regulatory domain. The canonical PARP inhibitor 3-aminobenzamide (3-AB), a nicotinamide mimic, is bound in the active site. The helical domain is shown in blue, and the transferase domain in green and orange. The structure has been deposited in PDB (PDB: 4F0D). Published in Karlberg et al. Journal of Biological Chemistry, 2012.

BiochemistryProteinsStructural Biology