9ETR: PARP1 catalytic domain

Crystal structure of PARP1 catalytic domain bound to AZD9574. Determined by X-ray diffraction at 1.82 Å resolution. Released 4 Dec 2024.

Method: X-ray diffraction
Resolution: 1.82 Å
Organism: Homo sapiens
Chains: 2
Atoms: 5,644
Mol. weight: 80.21 kDa
Ligands: A1H64
Released: 4 Dec 2024

Explore 9ETR in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9ETR contains 46 α-helices and 40 β-strands across 2 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 23 helices, 20 β-strands

Element	Residues	Length	Sheet
α-helix	667-676	10
α-helix	679-688	10
β-strand	691	1	1
α-helix	698-700	3
α-helix	703-721	19
α-helix	726-739	14
β-strand	742	1	1
α-helix	748-751	4
α-helix	755-779	25
α-helix	789-796	8
β-strand	799-803	5	2
α-helix	804-805	2
α-helix	809-820	12
α-helix	824-826	3
β-strand	829-841	13	2
α-helix	844-848	5
α-helix	849-851	3
β-strand	857-864	8	2
α-helix	866-868	3
α-helix	869-875	7
α-helix	879-881	3
α-helix	886-888	3
β-strand	895-897	3	3
β-strand	898	1	2
α-helix	901-905	5
α-helix	906-908	3
β-strand	911	1	4
β-strand	914	1	4
β-strand	916-925	10	2
β-strand	929-932	4	3
β-strand	936	1	5
α-helix	941-942	2
β-strand	947-950	4	3
β-strand	954-956	3	6
α-helix	958-960	3
β-strand	962-964	3	2
β-strand	967-969	3	2
α-helix	973	1
β-strand	974-976	3	6
β-strand	986	1	6
β-strand	988-991	4	3
α-helix	994-996	3
β-strand	997-1009	13	2

Chain B: 23 helices, 20 β-strands

Element	Residues	Length	Sheet
α-helix	667-676	10
α-helix	679-688	10
β-strand	691	1	7
α-helix	698-700	3
α-helix	703-722	20
α-helix	726-739	14
β-strand	742	1	7
α-helix	748-751	4
α-helix	755-779	25
α-helix	789-796	8
β-strand	799-803	5	8
α-helix	804-805	2
α-helix	809-820	12
α-helix	824-826	3
β-strand	829-841	13	8
α-helix	844-848	5
α-helix	849-851	3
β-strand	857-864	8	8
α-helix	866-868	3
α-helix	869-875	7
α-helix	879-881	3
α-helix	886-888	3
β-strand	895-897	3	9
β-strand	898	1	8
α-helix	901-905	5
α-helix	906-908	3
β-strand	911	1	10
β-strand	914	1	10
β-strand	916-925	10	8
β-strand	929-932	4	9
β-strand	936	1	5
α-helix	941-942	2
β-strand	947-950	4	9
β-strand	954-956	3	11
α-helix	958-960	3
β-strand	962-964	3	8
β-strand	967-969	3	8
α-helix	972-973	2
β-strand	974-976	3	11
β-strand	986	1	11
β-strand	988-991	4	9
α-helix	994-996	3
β-strand	997-1009	13	8

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Poly [ADP-ribose] polymerase 1, processed C-terminus	A, B	protein	355	Homo sapiens	P09874 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>9ETR_1 Poly [ADP-ribose] polymerase 1, processed C-terminus (chains A, B)
GPLGSKSKLPKPVQDLIKMIFDVESMKKAMVEYEIDLQKMPLGKLSKRQIQAAYSILSEV
QQAVSQGSSDSQILDLSNRFYTLIPHDFGMKKPPLLNNADSVQAKAEMLDNLLDIEVAYS
LLRGGSDDSSKDPIDVNYEKLKTDIKVVDRDSEEAEIIRKYVKNTHATTHNAYDLEVIDI
FKIEREGECQRYKPFKQLHNRRLLWHGSRTTNFAGILSQGLRIAPPEAPVTGYMFGKGIY
FADMVSKSANYCHTSQGDPIGLILLGEVALGNMYELKHASHISKLPKGKHSVKGLGKTTP
DPSANISLDGVDVPLGTGISSGVNDTSLLYNEYIVYDIAQVNLKYLLKLKFNFKT

Ligands and cofactors

ID	Name	Formula	Copies
A1H64	6-fluoranyl-5-[4-[(5-fluoranyl-2-methyl-3-oxidanylidene-4~{H}-quinoxalin-6-yl)m…	C21 H22 F2 N6 O2	2

Water and common crystallization additives (SO4) are not listed.

Primary citation

Discovery of 6-Fluoro-5-{4-[(5-fluoro-2-methyl-3-oxo-3,4-dihydroquinoxalin-6-yl)methyl]piperazin-1-yl}- N -methylpyridine-2-carboxamide (AZD9574): A CNS-Penetrant, PARP1-Selective Inhibitor. Johannes, J.W., Balazs, A.Y.S., Barratt, D. et al. J Med Chem (2024) 67:21717-21728. DOI 10.1021/acs.jmedchem.4c01725 · PubMed

Other PDB entries of the same protein (UniProt P09874 (AlphaFold model), which also has an AlphaFold model), best resolution first:

6NRH 1.5 Å, Crystal Structure of human PARP-1 ART domain bound inhibitor UTT63
9ETQ 1.59 Å, Crystal structure of PARP1 catalytic domain bound to AZD5305 (SARUPARIB)
7AAC 1.59 Å, Crystal structure of the catalytic domain of human PARP1 in complex with veliparib
6NRJ 1.65 Å, Crystal Structure of human PARP-1 ART domain bound to inhibitor UTT93
7KK2 1.7 Å, Structure of the catalytic domain of PARP1
2RIQ 1.7 Å, Crystal Structure of the Third Zinc-binding domain of human PARP-1
6NRG 1.7 Å, Crystal Structure of human PARP-1 ART domain bound to inhibitor UTT57
7KK5 1.7 Å, Structure of the catalytic domain of PARP1 in complex with niraparib
7AAA 1.74 Å, Crystal structure of the catalytic domain of human PARP1 (apo)
6NTU 1.8 Å, Crystal Structure of human PARP-1 ART domain bound to inhibitor UKTT-15
7ONT 1.85 Å, PARP1 catalytic domain in complex with a selective pyridine carboxamide-based inhibitor…
4ZZZ 1.9 Å, Structure of human PARP1 catalytic domain bound to an isoindolinone inhibitor

Browse structure collections

About this viewer

MolViewer shows 9ETR directly in your browser with nothing to install. Switch between cartoon, ball-and-stick, spacefill and surface views, color by chain, secondary structure or B-factor, measure distances, angles and dihedrals, and share or embed the view.