4XUC

Synthesis and evaluation of heterocyclic catechol mimics as inhibitors of catechol-O-methyltransferase (COMT): Structure with Cmpd18 (1-(biphenyl-3-yl)-3-hydroxypyridin-4(1H)-one)

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)
A	d4xuca_	Alpha and beta proteins (a/b)	S-adenosyl-L-methionine-dependent methyltransferases	S-adenosyl-L-methionine-dependent methyltransferases	COMT-like	Catechol O-methyltransferase, COMT	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)
A	SCOP2 Family	COMT-like	8078588	4000655	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	S-adenosyl-L-methionine-dependent methyltransferases	8078589	3000118	SCOP2 (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	Methyltransf_11_4	e4xucA1	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: S-adenosyl-L-methionine-dependent methyltransferases	F: Methyltransf_11_4	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.40.50.150	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Vaccinia Virus protein VP39	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF01596	O-methyltransferase (Methyltransf_3)	O-methyltransferase	Members of this family are O-methyltransferases. The family includes catechol o-methyltransferase Swiss:P21964, caffeoyl-CoA O-methyltransferase Swiss:Q43095 and a family of bacterial O-methyltransferases that may be involved in antibiotic production ...	Members of this family are O-methyltransferases. The family includes catechol o-methyltransferase Swiss:P21964, caffeoyl-CoA O-methyltransferase Swiss:Q43095 and a family of bacterial O-methyltransferases that may be involved in antibiotic production [1].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Catechol O-methyltransferase	transferase activity, transferring one-carbon groups transferase activity methyltransferase activity catalytic activity O-methyltransferase activity catechol O-methyltransferase activity S-adenosylmethionine-dependent methyltransferase activity cation binding magnesium ion binding ion binding binding metal ion binding small molecule binding	response to stimulus response to chemical response to xenobiotic stimulus multicellular organismal process renal system process system process renal filtration behavior exploration behavior methylation metabolic process cellular process monoamine transport regulation of biological process response to stimulus response to chemical response to xenobiotic stimulus multicellular organismal process renal system process system process renal filtration behavior exploration behavior methylation metabolic process cellular process monoamine transport regulation of biological process norepinephrine transport nitrogen compound transport transport secretion signaling biological regulation export from cell cell-cell signaling organic hydroxy compound transport establishment of localization organic cation transport cell communication catecholamine secretion localization secretion by cell catecholamine transport signal release norepinephrine secretion regulation of systemic arterial blood pressure by renin-angiotensin protein localization renin secretion into blood stream regulation of systemic arterial blood pressure by hormone regulation of systemic arterial blood pressure mediated by a chemical signal establishment of protein localization cellular localization protein localization to extracellular region circulatory system process renal response to blood flow involved in circulatory renin-angiotensin regulation of systemic arterial blood pressure cellular macromolecule localization renal system process involved in regulation of systemic arterial blood pressure regulation of biological quality blood circulation regulation of blood pressure establishment of protein localization to extracellular region regulation of systemic arterial blood pressure by circulatory renin-angiotensin protein secretion regulation of systemic arterial blood pressure endocrine process protein transport macromolecule localization prostaglandin metabolic process icosanoid metabolic process fatty acid metabolic process unsaturated fatty acid metabolic process oxoacid metabolic process carboxylic acid metabolic process primary metabolic process organic acid metabolic process prostanoid metabolic process small molecule metabolic process monocarboxylic acid metabolic process lipid metabolic process learning learning or memory nervous system process nonassociative learning cognition habituation response to angiotensin response to hormone response to endogenous stimulus response to peptide hormone response to oxygen-containing compound response to nitrogen compound developmental process multicellular organism development artery development anatomical structure development vasculature development blood vessel development system development circulatory system development cerebellum morphogenesis cerebellar cortex morphogenesis head development hindbrain morphogenesis animal organ development brain development nervous system development cerebellar cortex development anatomical structure morphogenesis cerebellum development central nervous system development metencephalon development hindbrain development memory catecholamine catabolic process catabolic process catechol-containing compound catabolic process organic hydroxy compound metabolic process catechol-containing compound metabolic process biogenic amine catabolic process phenol-containing compound catabolic process amine metabolic process catecholamine metabolic process organic hydroxy compound catabolic process phenol-containing compound metabolic process biogenic amine metabolic process amine catabolic process renal absorption renal albumin absorption renal protein absorption response to toxic substance dopamine metabolic process response to ketone response to lipid response to alcohol response to glucocorticoid response to corticosterone response to mineralocorticoid response to corticosteroid response to steroid hormone response to organic cyclic compound startle response neuromuscular process response to external stimulus detection of external stimulus detection of stimulus involved in sensory perception of pain sensory perception of temperature stimulus sensory perception of pain detection of temperature stimulus involved in sensory perception response to temperature stimulus detection of abiotic stimulus detection of stimulus sensory perception detection of temperature stimulus response to abiotic stimulus detection of stimulus involved in sensory perception detection of temperature stimulus involved in sensory perception of pain response to salt trans-synaptic signaling chemical synaptic transmission synaptic signaling anterograde trans-synaptic signaling synaptic transmission, dopaminergic response to stress response to wounding lipid localization cholesterol transport lipid transport sterol transport cholesterol efflux response to decreased oxygen levels response to hypoxia response to oxygen levels glomerulus development nephron development kidney development renal system development multicellular organism growth developmental growth growth excretion renal sodium excretion sodium ion homeostasis inorganic ion homeostasis homeostatic process renal tubular secretion chemical homeostasis monoatomic ion homeostasis monoatomic cation homeostasis digestion digestive system process mastication response to peptide response to cytokine response to light stimulus visual learning visual behavior associative learning response to radiation biosynthetic process macromolecule metabolic process gene expression macromolecule biosynthetic process response to dopamine response to catecholamine response to monoamine norepinephrine metabolic process cellular response to nitrogen compound cellular response to stimulus cellular response to organic cyclic compound cellular response to oxygen-containing compound response to alkaloid cellular response to chemical stimulus cellular response to cocaine cellular response to alkaloid response to cocaine response to amine response to amphetamine behavioral defense response fear response behavioral fear response defense response multicellular organismal response to stress response to oxidative stress cellular response to nutrient levels response to nutrient levels cellular response to phosphate starvation cellular response to stress response to starvation cellular response to starvation dopamine catabolic process response to food carbohydrate metabolic process energy derivation by oxidation of organic compounds glycogen metabolic process generation of precursor metabolites and energy glucan metabolic process polysaccharide metabolic process energy reserve metabolic process dopamine secretion dopamine transport	cellular anatomical structure membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm cytosol cellular anatomical structure membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm cytosol somatodendritic compartment cell projection dendrite dendritic tree neuron projection plasma membrane bounded cell projection axon cell periphery plasma membrane intracellular organelle intracellular membrane-bounded organelle synapse cell junction

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR002935	Class I-like SAM-dependent O-methyltransferase	Family
A	IPR029063	S-adenosyl-L-methionine-dependent methyltransferase superfamily	Homologous Superfamily
A	IPR017128	Catechol O-methyltransferase, eukaryotic	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P21964	schizophrenia DiGeorge syndrome alcohol abuse breast carcinoma cocaine abuse Cognition Disorders velocardiofacial syndrome panic disorder bipolar disorder cocaine dependence amphetamine abuse hearing loss, cisplatin-induced, susceptibility to attention deficit hyperactivity disorder, inattentive type Parkinson disease prostate cancer schizophrenia DiGeorge syndrome alcohol abuse breast carcinoma cocaine abuse Cognition Disorders velocardiofacial syndrome panic disorder bipolar disorder cocaine dependence amphetamine abuse hearing loss, cisplatin-induced, susceptibility to attention deficit hyperactivity disorder, inattentive type Parkinson disease prostate cancer major depressive disorder autism phaeochromocytoma biliary dyskinesia mammary neoplasms, animal adrenal gland pheochromocytoma depressive disorder mood disorder extra-adrenal sympathetic paraganglioma open-angle glaucoma fibromyalgia anxiety disorder malignant ependymoma psychiatric disorder tuberculosis fetal growth restriction opiate dependence malignant mesothelioma breast cancer temporomandibular joint disorder ovarian cancer hepatocellular carcinoma

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.