1UK0

Crystal structure of catalytic domain of human poly(ADP-ribose) polymerase with a novel inhibitor

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
B	d1uk0b1	All alpha proteins	Domain of poly(ADP-ribose) polymerase	Domain of poly(ADP-ribose) polymerase	Domain of poly(ADP-ribose) polymerase	Domain of poly(ADP-ribose) polymerase	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d1uk0b2	Alpha and beta proteins (a+b)	ADP-ribosylation	ADP-ribosylation	Poly(ADP-ribose) polymerase, C-terminal domain	Poly(ADP-ribose) polymerase, C-terminal domain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d1uk0a1	All alpha proteins	Domain of poly(ADP-ribose) polymerase	Domain of poly(ADP-ribose) polymerase	Domain of poly(ADP-ribose) polymerase	Domain of poly(ADP-ribose) polymerase	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d1uk0a2	Alpha and beta proteins (a+b)	ADP-ribosylation	ADP-ribosylation	Poly(ADP-ribose) polymerase, C-terminal domain	Poly(ADP-ribose) polymerase, C-terminal domain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
B	SCOP2B Superfamily	Domain of poly(ADP-ribose) polymerase	8036812	3000280	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	ADP-ribosylation	8036814	3001208	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	ADP-ribosylation	8036814	3001208	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Domain of poly(ADP-ribose) polymerase	8036812	3000280	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
B	PARP_reg	e1uk0B1	A: alpha bundles	X: Domain of poly(ADP-ribose) polymerase (From Topology)	H: Domain of poly(ADP-ribose) polymerase (From Topology)	T: Domain of poly(ADP-ribose) polymerase	F: PARP_reg	ECOD (1.6)
B	PARP	e1uk0B2	A: a+b complex topology	X: ADP-ribosylation (From Topology)	H: ADP-ribosylation (From Topology)	T: ADP-ribosylation	F: PARP	ECOD (1.6)
A	PARP_reg	e1uk0A1	A: alpha bundles	X: Domain of poly(ADP-ribose) polymerase (From Topology)	H: Domain of poly(ADP-ribose) polymerase (From Topology)	T: Domain of poly(ADP-ribose) polymerase	F: PARP_reg	ECOD (1.6)
A	PARP	e1uk0A2	A: a+b complex topology	X: ADP-ribosylation (From Topology)	H: ADP-ribosylation (From Topology)	T: ADP-ribosylation	F: PARP	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
B	1.20.142.10	Mainly Alpha	Up-down Bundle	Poly(ADP-ribose) Polymerase	domain 1	CATH (4.3.0)
B	3.90.228.10	Alpha Beta	Alpha-Beta Complex	Phosphoenolpyruvate Carboxykinase	domain 3	CATH (4.3.0)
A	1.20.142.10	Mainly Alpha	Up-down Bundle	Poly(ADP-ribose) Polymerase	domain 1	CATH (4.3.0)
A	3.90.228.10	Alpha Beta	Alpha-Beta Complex	Phosphoenolpyruvate Carboxykinase	domain 3	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF00644	Poly(ADP-ribose) polymerase catalytic domain (PARP)	Poly(ADP-ribose) polymerase catalytic domain	-	Family
A, B	PF02877	Poly(ADP-ribose) polymerase, regulatory domain (PARP_reg)	Poly(ADP-ribose) polymerase, regulatory domain	Poly(ADP-ribose) polymerase catalyses the covalent attachment of ADP-ribose units from NAD+ to itself and to a limited number of other DNA binding proteins, which decreases their affinity for DNA. Poly(ADP-ribose) polymerase is a regulatory component ...	Poly(ADP-ribose) polymerase catalyses the covalent attachment of ADP-ribose units from NAD+ to itself and to a limited number of other DNA binding proteins, which decreases their affinity for DNA. Poly(ADP-ribose) polymerase is a regulatory component induced by DNA damage. The carboxyl-terminal region is the most highly conserved region of the protein. Experiments have shown that a carboxyl 40 kDa fragment is still catalytically active [2].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	Poly [ADP-ribose] polymerase-1	NAD+-protein-serine ADP-ribosyltransferase activity pentosyltransferase activity catalytic activity, acting on a protein glycosyltransferase activity NAD+-histone H3S10 serine ADP-ribosyltransferase activity NAD+-protein ADP-ribosyltransferase activity transferase activity catalytic activity histone deacetylase binding protein binding binding enzyme binding DNA binding organic cyclic compound binding NAD+-protein-serine ADP-ribosyltransferase activity pentosyltransferase activity catalytic activity, acting on a protein glycosyltransferase activity NAD+-histone H3S10 serine ADP-ribosyltransferase activity NAD+-protein ADP-ribosyltransferase activity transferase activity catalytic activity histone deacetylase binding protein binding binding enzyme binding DNA binding organic cyclic compound binding nucleic acid binding ubiquitin protein ligase binding ubiquitin-like protein ligase binding NAD binding nucleoside phosphate binding purine nucleotide binding adenyl nucleotide binding nucleotide binding heterocyclic compound binding small molecule binding NAD+-histone H2BS6 serine ADP-ribosyltransferase activity identical protein binding protein homodimerization activity protein dimerization activity kinase binding protein kinase binding NAD+-protein-aspartate ADP-ribosyltransferase activity NAD+-histone H2BE35 glutamate ADP-ribosyltransferase activity NAD+-protein-glutamate ADP-ribosyltransferase activity nucleotidyltransferase activity transferase activity, transferring phosphorus-containing groups transcription factor binding RNA polymerase II-specific DNA-binding transcription factor binding nuclear receptor binding DNA-binding transcription factor binding nuclear estrogen receptor binding NAD+-protein-histidine ADP-ribosyltransferase activity SMAD binding R-SMAD binding NAD+-protein poly-ADP-ribosyltransferase activity NAD+-protein-tyrosine ADP-ribosyltransferase activity NAD DNA ADP-ribosyltransferase activity molecular function activator activity molecular function regulator activity transcription regulator activator activity chromatin binding RNA binding damaged DNA binding cation binding transition metal ion binding zinc ion binding ion binding metal ion binding protein-containing complex binding nucleosome binding	cellular response to stimulus positive regulation of cell communication cell surface receptor protein serine/threonine kinase signaling pathway regulation of cellular process positive regulation of signal transduction response to stimulus signaling regulation of transmembrane receptor protein serine/threonine kinase signaling pathway positive regulation of biological process regulation of signal transduction intracellular signal transduction cell communication positive regulation of response to stimulus regulation of intracellular signal transduction intracellular signaling cassette cellular response to stimulus positive regulation of cell communication cell surface receptor protein serine/threonine kinase signaling pathway regulation of cellular process positive regulation of signal transduction response to stimulus signaling regulation of transmembrane receptor protein serine/threonine kinase signaling pathway positive regulation of biological process regulation of signal transduction intracellular signal transduction cell communication positive regulation of response to stimulus regulation of intracellular signal transduction intracellular signaling cassette signal transduction enzyme-linked receptor protein signaling pathway positive regulation of cellular process regulation of biological process regulation of signaling cell surface receptor signaling pathway biological regulation positive regulation of intracellular signal transduction positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway SMAD protein signal transduction regulation of response to stimulus regulation of cell communication cellular process regulation of SMAD protein signal transduction positive regulation of SMAD protein signal transduction positive regulation of signaling macromolecule modification metabolic process primary metabolic process protein metabolic process macromolecule metabolic process protein modification process apoptotic process cell death programmed cell death carbohydrate metabolic process biosynthetic process carbohydrate biosynthetic process single strand break repair regulation of cellular response to stress positive regulation of single strand break repair regulation of primary metabolic process nucleobase-containing compound metabolic process positive regulation of metabolic process positive regulation of DNA repair cellular response to stress response to stress regulation of response to stress positive regulation of macromolecule metabolic process regulation of nucleobase-containing compound metabolic process DNA repair positive regulation of nucleobase-containing compound metabolic process regulation of single strand break repair DNA metabolic process regulation of macromolecule metabolic process nucleic acid metabolic process regulation of DNA repair positive regulation of DNA metabolic process DNA damage response regulation of metabolic process regulation of DNA metabolic process response to oxidative stress cellular response to chemical stimulus response to chemical cellular response to oxidative stress cellular response to chemical stress regulation of DNA recombination regulation of double-strand break repair positive regulation of double-strand break repair via homologous recombination recombinational repair double-strand break repair via homologous recombination positive regulation of DNA recombination double-strand break repair DNA recombination positive regulation of double-strand break repair regulation of double-strand break repair via homologous recombination circadian sleep/wake cycle, sleep rhythmic process multicellular organismal process circadian sleep/wake cycle rhythmic behavior circadian rhythm regulation of circadian sleep/wake cycle regulation of circadian sleep/wake cycle, non-REM sleep regulation of circadian rhythm circadian sleep/wake cycle, non-REM sleep behavior regulation of behavior circadian behavior sleep regulation of multicellular organismal process regulation of circadian sleep/wake cycle, sleep circadian sleep/wake cycle process regulation of biosynthetic process gene expression macromolecule biosynthetic process regulation of gene expression signal transduction involved in regulation of gene expression regulation of macromolecule biosynthetic process muscle hypertrophy regulation of muscle adaptation system process positive regulation of cardiac muscle hypertrophy regulation of system process striated muscle hypertrophy regulation of muscle system process muscle system process regulation of cardiac muscle hypertrophy regulation of muscle hypertrophy muscle adaptation positive regulation of muscle hypertrophy cardiac muscle hypertrophy positive regulation of multicellular organismal process regulation of base-excision repair base-excision repair negative regulation of biological process RNA metabolic process negative regulation of RNA biosynthetic process RNA biosynthetic process DNA-templated transcription nucleic acid biosynthetic process regulation of RNA metabolic process transcription by RNA polymerase II negative regulation of cellular process negative regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process negative regulation of macromolecule metabolic process regulation of transcription by RNA polymerase II negative regulation of DNA-templated transcription negative regulation of transcription by RNA polymerase II negative regulation of metabolic process nucleobase-containing compound biosynthetic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process regulation of DNA-templated transcription negative regulation of RNA metabolic process positive regulation of response to biotic stimulus pattern recognition receptor signaling pathway response to biotic stimulus cGAS/STING signaling pathway immune response-activating signaling pathway positive regulation of immune response regulation of immune system process positive regulation of immune system process innate immune response-activating signaling pathway immune response response to other organism regulation of innate immune response response to external stimulus negative regulation of cGAS/STING signaling pathway defense response to other organism regulation of pattern recognition receptor signaling pathway positive regulation of defense response activation of innate immune response regulation of immune response activation of immune response cytoplasmic pattern recognition receptor signaling pathway regulation of defense response regulation of response to biotic stimulus biological process involved in interspecies interaction between organisms regulation of response to external stimulus intracellular receptor signaling pathway negative regulation of signaling negative regulation of cytoplasmic pattern recognition receptor signaling pathway negative regulation of intracellular signal transduction regulation of cytoplasmic pattern recognition receptor signaling pathway negative regulation of cell communication positive regulation of response to external stimulus immune response-regulating signaling pathway innate immune response response to external biotic stimulus positive regulation of innate immune response defense response negative regulation of response to stimulus defense response to symbiont negative regulation of signal transduction negative regulation of immune system process immune system process cellular response to growth factor stimulus cellular response to transforming growth factor beta stimulus response to endogenous stimulus cellular response to endogenous stimulus response to transforming growth factor beta transforming growth factor beta receptor signaling pathway response to growth factor transforming growth factor beta receptor superfamily signaling pathway DNA modification DNA ADP-ribosylation positive regulation of canonical NF-kappaB signal transduction canonical NF-kappaB signal transduction regulation of canonical NF-kappaB signal transduction positive regulation of DNA-templated transcription positive regulation of macromolecule biosynthetic process positive regulation of DNA-templated transcription, elongation positive regulation of biosynthetic process regulation of DNA-templated transcription elongation positive regulation of RNA metabolic process DNA-templated transcription elongation positive regulation of RNA biosynthetic process DNA-templated DNA replication DNA-templated DNA replication maintenance of fidelity replication fork reversal DNA replication replication fork processing developmental process myeloid leukocyte differentiation cellular developmental process hemopoiesis macrophage differentiation cell development mononuclear cell differentiation myeloid cell differentiation cell differentiation anatomical structure development leukocyte differentiation protein localization regulation of localization cellular localization regulation of protein localization localization regulation of cellular localization cellular macromolecule localization macromolecule localization cellular response to metal ion response to metal ion response to zinc ion cellular response to zinc ion multi-multicellular organism process placenta development reproductive process maternal process involved in female pregnancy multicellular organismal reproductive process animal organ development developmental process involved in reproduction tissue development maternal placenta development female pregnancy multi-organism reproductive process decidualization response to ionizing radiation response to radiation response to abiotic stimulus response to gamma radiation regulation of telomere maintenance negative regulation of telomere maintenance regulation of cellular component organization negative regulation of telomere maintenance via telomere lengthening telomere organization telomere maintenance via telomere lengthening cellular component organization negative regulation of chromosome organization cellular component organization or biogenesis negative regulation of cellular component organization chromosome organization regulation of chromosome organization regulation of telomere maintenance via telomere lengthening regulation of organelle organization telomere maintenance organelle organization negative regulation of organelle organization negative regulation of DNA metabolic process positive regulation of programmed cell death positive regulation of necroptotic process necroptotic process programmed necrotic cell death regulation of programmed cell death regulation of necroptotic process regulation of programmed necrotic cell death positive regulation of programmed necrotic cell death cellular response to nitrogen compound response to peptide hormone response to oxygen-containing compound cellular response to peptide hormone stimulus response to nitrogen compound cellular response to oxygen-containing compound response to hormone response to insulin cellular response to insulin stimulus cellular response to hormone stimulus response to lipid positive regulation of intracellular estrogen receptor signaling pathway hormone-mediated signaling pathway response to steroid hormone regulation of intracellular estrogen receptor signaling pathway regulation of intracellular steroid hormone receptor signaling pathway nuclear receptor-mediated steroid hormone signaling pathway cellular response to steroid hormone stimulus response to organic cyclic compound steroid hormone receptor signaling pathway cellular response to organic cyclic compound estrogen receptor signaling pathway positive regulation of intracellular steroid hormone receptor signaling pathway cellular response to lipid nuclear receptor-mediated signaling pathway protein auto-ADP-ribosylation post-translational protein modification cellular response to amyloid-beta response to amyloid-beta protein maturation protein autoprocessing proteolysis protein processing transcription elongation by RNA polymerase II negative regulation of transcription elongation by RNA polymerase II regulation of transcription elongation by RNA polymerase II negative regulation of DNA-templated transcription, elongation regulation of mitochondrial depolarization positive regulation of membrane depolarization positive regulation of mitochondrial depolarization mitochondrial depolarization regulation of membrane depolarization regulation of mitochondrial membrane potential membrane depolarization regulation of biological quality regulation of membrane potential cellular response to nerve growth factor stimulus response to nerve growth factor ribose phosphate metabolic process ATP metabolic process carbohydrate derivative metabolic process ATP generation from poly-ADP-D-ribose purine nucleotide metabolic process ribonucleotide metabolic process nucleobase-containing small molecule metabolic process purine ribonucleoside triphosphate metabolic process phosphate-containing compound metabolic process small molecule metabolic process phosphorus metabolic process ribonucleoside triphosphate metabolic process nucleoside phosphate metabolic process purine nucleoside triphosphate metabolic process nucleotide metabolic process purine-containing compound metabolic process organophosphate metabolic process nucleoside triphosphate metabolic process purine ribonucleotide metabolic process negative regulation of adipose tissue development regulation of developmental process connective tissue development adipose tissue development negative regulation of developmental process regulation of adipose tissue development negative regulation of multicellular organismal process intrinsic apoptotic signaling pathway in response to oxidative stress neuron apoptotic process regulation of oxidative stress-induced intrinsic apoptotic signaling pathway regulation of intrinsic apoptotic signaling pathway intrinsic apoptotic signaling pathway regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway regulation of apoptotic process neuron intrinsic apoptotic signaling pathway in response to oxidative stress apoptotic signaling pathway regulation of neuron apoptotic process regulation of apoptotic signaling pathway positive regulation of myofibroblast differentiation regulation of cell differentiation regulation of myofibroblast differentiation myofibroblast differentiation positive regulation of developmental process positive regulation of cell differentiation response to aldosterone response to ketone response to alcohol response to mineralocorticoid response to corticosteroid mitochondrial genome maintenance mitochondrial DNA metabolic process mitochondrion organization positive regulation of transcription by RNA polymerase II negative regulation of small molecule metabolic process nucleotide biosynthetic process purine ribonucleotide biosynthetic process negative regulation of ATP metabolic process purine ribonucleoside triphosphate biosynthetic process regulation of nucleotide biosynthetic process regulation of ATP metabolic process ribonucleotide biosynthetic process negative regulation of nucleotide metabolic process purine nucleoside triphosphate biosynthetic process regulation of small molecule metabolic process negative regulation of nucleotide biosynthetic process regulation of nucleotide metabolic process regulation of phosphate metabolic process ribose phosphate biosynthetic process regulation of purine nucleotide metabolic process ribonucleoside triphosphate biosynthetic process organophosphate biosynthetic process nucleoside phosphate biosynthetic process regulation of phosphorus metabolic process purine nucleotide biosynthetic process negative regulation of purine nucleotide metabolic process ATP biosynthetic process negative regulation of phosphate metabolic process negative regulation of ATP biosynthetic process negative regulation of purine nucleotide biosynthetic process purine-containing compound biosynthetic process carbohydrate derivative biosynthetic process regulation of purine nucleotide biosynthetic process nucleoside triphosphate biosynthetic process regulation of ATP biosynthetic process negative regulation of phosphorus metabolic process positive regulation of protein localization to nucleus regulation of protein localization to nucleus protein localization to nucleus protein localization to organelle positive regulation of protein localization protein localization to chromatin protein localization to chromosome negative regulation of response to biotic stimulus negative regulation of immune response negative regulation of response to external stimulus negative regulation of defense response negative regulation of innate immune response regulation of molecular function regulation of catalytic activity response to light stimulus cellular response to radiation response to UV cellular response to environmental stimulus cellular response to light stimulus cellular response to abiotic stimulus cellular response to UV mitochondrial DNA repair protein poly-ADP-ribosylation	membrane-bounded organelle intracellular organelle organelle envelope cellular anatomical structure intracellular anatomical structure organelle nuclear envelope nucleus intracellular membrane-bounded organelle endomembrane system cytoplasm cytosol membrane-enclosed lumen nuclear replication fork membrane-bounded organelle intracellular organelle organelle envelope cellular anatomical structure intracellular anatomical structure organelle nuclear envelope nucleus intracellular membrane-bounded organelle endomembrane system cytoplasm cytosol membrane-enclosed lumen nuclear replication fork intracellular membraneless organelle nuclear chromosome chromosome intracellular organelle lumen organelle lumen membraneless organelle replication fork nuclear lumen nucleolus protein-containing complex site of double-strand break site of DNA damage nuclear body nucleoplasm membrane transcription regulator complex chromatin chromosome, telomeric region chromosomal region mitochondrion protein-DNA complex

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR038650	PADR1, C-terminal domain superfamily	Homologous Superfamily
A, B	IPR050800	ADP-ribosyltransferase diphtheria toxin-like	Family
A, B	IPR001510	Zinc finger, PARP-type	Domain
A, B	IPR012982	PARP1-like, PADR1 domain, zinc ribbon fold	Domain
A, B	IPR049296	PARP1-like, PADR1 domain, N-terminal helical subdomain	Domain
A, B	IPR012317	Poly(ADP-ribose) polymerase, catalytic domain	Domain
A, B	IPR036957	Zinc finger, PARP-type superfamily	Homologous Superfamily
A, B	IPR001357	BRCT domain	Domain
A, B	IPR036930	WGR domain superfamily	Homologous Superfamily
A, B	IPR008893	WGR domain	Domain
A, B	IPR036420	BRCT domain superfamily	Homologous Superfamily
A, B	IPR036616	Poly(ADP-ribose) polymerase, regulatory domain superfamily	Homologous Superfamily
A, B	IPR004102	Poly(ADP-ribose) polymerase, regulatory domain	Domain
A, B	IPR008288	Poly [ADP-ribose] polymerase	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: P09874	Stevens-Johnson syndrome intellectual disability melanoma plasma cell myeloma malignant mesothelioma cardiomyopathy breast carcinoma vitamin A deficiency alopecia dermatitis anemia ovarian cancer asthma atherosclerosis hepatitis Stevens-Johnson syndrome intellectual disability melanoma plasma cell myeloma malignant mesothelioma cardiomyopathy breast carcinoma vitamin A deficiency alopecia dermatitis anemia ovarian cancer asthma atherosclerosis hepatitis pneumonia prostate cancer pulmonary fibrosis Ceroid lipofuscinosis, neuronal 1, infantile breast cancer colorectal cancer cutaneous melanoma obesity disorder brain ischemia kidney disease large cell medulloblastoma lung cancer colorectal carcinoma parkinsonian disorder autosomal recessive juvenile Parkinson disease 2 idiopathic interstitial pneumonia breast disease non-small cell lung carcinoma ovarian disease peripheral nervous system disease brain injury invasive ductal breast carcinoma pneumonitis lung adenocarcinoma cancer toxic epidermal necrolysis myeloid neoplasm androgenetic alopecia arteriosclerosis disorder ovarian epithelial tumor peripheral neuropathy plasma cell neoplasm

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.