4V3U

Structure of human nNOS R354A G357D mutant heme domain in complex with N-2-(2-(1H-imidazol-1-yl)pyrimidin-4-yl)ethyl-3-(pyridin-3-yl) propan-1-amine

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	d4v3ua_	Alpha and beta proteins (a+b)	Nitric oxide (NO) synthase oxygenase domain	Nitric oxide (NO) synthase oxygenase domain	Nitric oxide (NO) synthase oxygenase domain	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d4v3ub_	Alpha and beta proteins (a+b)	Nitric oxide (NO) synthase oxygenase domain	Nitric oxide (NO) synthase oxygenase domain	Nitric oxide (NO) synthase oxygenase domain	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d4v3ud_	Alpha and beta proteins (a+b)	Nitric oxide (NO) synthase oxygenase domain	Nitric oxide (NO) synthase oxygenase domain	Nitric oxide (NO) synthase oxygenase domain	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d4v3uc_	Alpha and beta proteins (a+b)	Nitric oxide (NO) synthase oxygenase domain	Nitric oxide (NO) synthase oxygenase domain	Nitric oxide (NO) synthase oxygenase domain	automated matches	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	SCOP2B Superfamily	Nitric oxide (NO) synthase oxygenase domain	8079787	3001407	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Nitric oxide (NO) synthase oxygenase domain	8079787	3001407	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Nitric oxide (NO) synthase oxygenase domain	8079787	3001407	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Nitric oxide (NO) synthase oxygenase domain	8079787	3001407	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)
A	NO_synthase	e4v3uA1	A: a+b complex topology	X: Nitric oxide (NO) synthase oxygenase domain (From Topology)	H: Nitric oxide (NO) synthase oxygenase domain (From Topology)	T: Nitric oxide (NO) synthase oxygenase domain	F: NO_synthase	ECOD (1.6)
B	NO_synthase	e4v3uB1	A: a+b complex topology	X: Nitric oxide (NO) synthase oxygenase domain (From Topology)	H: Nitric oxide (NO) synthase oxygenase domain (From Topology)	T: Nitric oxide (NO) synthase oxygenase domain	F: NO_synthase	ECOD (1.6)
D	NO_synthase	e4v3uD1	A: a+b complex topology	X: Nitric oxide (NO) synthase oxygenase domain (From Topology)	H: Nitric oxide (NO) synthase oxygenase domain (From Topology)	T: Nitric oxide (NO) synthase oxygenase domain	F: NO_synthase	ECOD (1.6)
C	NO_synthase	e4v3uC1	A: a+b complex topology	X: Nitric oxide (NO) synthase oxygenase domain (From Topology)	H: Nitric oxide (NO) synthase oxygenase domain (From Topology)	T: Nitric oxide (NO) synthase oxygenase domain	F: NO_synthase	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.90.340.10	Alpha Beta	Alpha-Beta Complex	Nitric Oxide Synthase	Chain A, domain 1	CATH (4.3.0)
A	3.90.440.10	Alpha Beta	Alpha-Beta Complex	Nitric Oxide Synthase	Heme Domain	CATH (4.3.0)
A	3.90.1230.10	Alpha Beta	Alpha-Beta Complex	Bovine Endothelial Nitric Oxide Synthase Heme Domain	Chain: A,domain 3	CATH (4.3.0)
B	3.90.340.10	Alpha Beta	Alpha-Beta Complex	Nitric Oxide Synthase	Chain A, domain 1	CATH (4.3.0)
B	3.90.440.10	Alpha Beta	Alpha-Beta Complex	Nitric Oxide Synthase	Heme Domain	CATH (4.3.0)
B	3.90.1230.10	Alpha Beta	Alpha-Beta Complex	Bovine Endothelial Nitric Oxide Synthase Heme Domain	Chain: A,domain 3	CATH (4.3.0)
D	3.90.340.10	Alpha Beta	Alpha-Beta Complex	Nitric Oxide Synthase	Chain A, domain 1	CATH (4.3.0)
D	3.90.440.10	Alpha Beta	Alpha-Beta Complex	Nitric Oxide Synthase	Heme Domain	CATH (4.3.0)
D	3.90.1230.10	Alpha Beta	Alpha-Beta Complex	Bovine Endothelial Nitric Oxide Synthase Heme Domain	Chain: A,domain 3	CATH (4.3.0)
C	3.90.340.10	Alpha Beta	Alpha-Beta Complex	Nitric Oxide Synthase	Chain A, domain 1	CATH (4.3.0)
C	3.90.440.10	Alpha Beta	Alpha-Beta Complex	Nitric Oxide Synthase	Heme Domain	CATH (4.3.0)
C	3.90.1230.10	Alpha Beta	Alpha-Beta Complex	Bovine Endothelial Nitric Oxide Synthase Heme Domain	Chain: A,domain 3	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D	PF02898	Nitric oxide synthase, oxygenase domain (NO_synthase)	Nitric oxide synthase, oxygenase domain	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D	NITRIC OXIDE SYNTHASE, BRAIN	binding nucleotide binding FMN binding nucleoside phosphate binding ion binding organic cyclic compound binding anion binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding flavin adenine dinucleotide binding cation binding organic acid binding binding nucleotide binding FMN binding nucleoside phosphate binding ion binding organic cyclic compound binding anion binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding flavin adenine dinucleotide binding cation binding organic acid binding amino acid binding carboxylic acid binding arginine binding channel regulator activity ion channel regulator activity calcium channel regulator activity molecular function regulator activity transporter regulator activity transition metal ion binding cadmium ion binding metal ion binding oxidoreductase activity monooxygenase activity oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen nitric-oxide synthase activity oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen catalytic activity protein binding calmodulin binding tetrahydrobiopterin binding scaffold protein binding transmembrane transporter binding purine nucleotide binding adenyl nucleotide binding NADP binding sodium channel regulator activity tetrapyrrole binding heme binding calcium-dependent protein binding	multicellular organismal process system process muscle contraction muscle system process striated muscle contraction heart process regulation of biological process regulation of heart contraction regulation of system process biological regulation circulatory system process regulation of blood circulation positive regulation of the force of heart contraction regulation of multicellular organismal process multicellular organismal process system process muscle contraction muscle system process striated muscle contraction heart process regulation of biological process regulation of heart contraction regulation of system process biological regulation circulatory system process regulation of blood circulation positive regulation of the force of heart contraction regulation of multicellular organismal process regulation of biological quality heart contraction regulation of the force of heart contraction blood circulation cardiac muscle cell membrane repolarization cardiac muscle cell action potential involved in contraction regulation of membrane repolarization during action potential membrane repolarization membrane repolarization during cardiac muscle cell action potential ventricular cardiac muscle cell membrane repolarization positive regulation of biological process positive regulation of membrane repolarization during cardiac muscle cell action potential positive regulation of membrane repolarization during ventricular cardiac muscle cell action potential cardiac muscle contraction regulation of membrane repolarization during ventricular cardiac muscle cell action potential regulation of membrane repolarization during cardiac muscle cell action potential actin filament-based process regulation of action potential cardiac muscle cell contraction regulation of cardiac muscle cell membrane repolarization ventricular cardiac muscle cell action potential action potential actin filament-based movement membrane repolarization during action potential regulation of membrane repolarization cellular process membrane repolarization during ventricular cardiac muscle cell action potential cardiac muscle cell action potential actin-mediated cell contraction regulation of ventricular cardiac muscle cell membrane repolarization regulation of membrane potential regulation of cellular process positive regulation of phosphorylation regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process regulation of peptidyl-serine phosphorylation positive regulation of phosphate metabolic process peptidyl-serine modification regulation of primary metabolic process positive regulation of metabolic process positive regulation of protein modification process peptidyl-serine phosphorylation regulation of phosphate metabolic process phosphate-containing compound metabolic process peptidyl-amino acid modification positive regulation of macromolecule metabolic process protein metabolic process positive regulation of protein phosphorylation phosphorus metabolic process protein modification process positive regulation of cellular process protein phosphorylation positive regulation of phosphorus metabolic process phosphorylation regulation of protein metabolic process primary metabolic process regulation of macromolecule metabolic process positive regulation of peptidyl-serine phosphorylation macromolecule modification regulation of phosphorus metabolic process metabolic process regulation of phosphorylation macromolecule metabolic process regulation of metabolic process catabolic process oxoacid metabolic process glutamine family amino acid catabolic process amino acid metabolic process arginine catabolic process organic acid metabolic process organic acid catabolic process alpha-amino acid metabolic process glutamine family amino acid metabolic process cellular catabolic process arginine metabolic process carboxylic acid catabolic process small molecule metabolic process amino acid catabolic process carboxylic acid metabolic process L-amino acid catabolic process L-amino acid metabolic process proteinogenic amino acid metabolic process alpha-amino acid catabolic process proteinogenic amino acid catabolic process small molecule catabolic process response to stimulus response to stress multicellular organismal response to stress cellular response to stimulus positive regulation of cell communication positive regulation of signal transduction signaling regulation of signal transduction cell communication positive regulation of response to stimulus positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway signal transduction regulation of G protein-coupled receptor signaling pathway regulation of signaling adenylate cyclase-activating G protein-coupled receptor signaling pathway positive regulation of G protein-coupled receptor signaling pathway regulation of response to stimulus adenylate cyclase-modulating G protein-coupled receptor signaling pathway regulation of cell communication G protein-coupled receptor signaling pathway regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway positive regulation of signaling regulation of localization regulation of calcium ion transport transport regulation of transport negative regulation of monoatomic ion transport regulation of monoatomic ion transport negative regulation of biological process negative regulation of transport establishment of localization calcium ion transport metal ion transport negative regulation of calcium ion transport localization monoatomic ion transport monoatomic cation transport regulation of metal ion transport cellular response to xenobiotic stimulus xenobiotic catabolic process xenobiotic metabolic process response to xenobiotic stimulus cellular response to chemical stimulus response to chemical cell redox homeostasis cellular homeostasis homeostatic process developmental process cellular developmental process myoblast fusion cell-cell fusion muscle cell differentiation myotube differentiation muscle structure development syncytium formation by plasma membrane fusion anatomical structure morphogenesis cell differentiation anatomical structure formation involved in morphogenesis anatomical structure development syncytium formation striated muscle cell differentiation response to decreased oxygen levels response to hypoxia response to oxygen levels response to abiotic stimulus monoatomic ion transmembrane transport regulation of monoatomic ion transmembrane transport regulation of calcium ion transmembrane transport monoatomic cation transmembrane transport regulation of calcium ion transmembrane transport via high voltage-gated calcium channel calcium ion transmembrane transport via high voltage-gated calcium channel inorganic ion transmembrane transport inorganic cation transmembrane transport transmembrane transport regulation of transmembrane transport regulation of monoatomic cation transmembrane transport calcium ion transmembrane transport response to heat response to temperature stimulus cellular localization regulation of calcium ion transport into cytosol negative regulation of transmembrane transport negative regulation of monoatomic ion transmembrane transport negative regulation of cellular process negative regulation of cation transmembrane transport negative regulation of calcium ion transport into cytosol calcium ion transmembrane import into cytosol positive regulation of cytosolic calcium ion concentration regulation of cellular localization negative regulation of calcium ion transmembrane transport negative regulation of cytosolic calcium ion concentration calcium ion transport into cytosol positive regulation of DNA-templated transcription RNA metabolic process positive regulation of macromolecule biosynthetic process nucleobase-containing compound metabolic process RNA biosynthetic process nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process transcription by RNA polymerase II positive regulation of biosynthetic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of biosynthetic process regulation of transcription by RNA polymerase II positive regulation of nucleobase-containing compound metabolic process positive regulation of transcription by RNA polymerase II nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process positive regulation of RNA metabolic process regulation of gene expression biosynthetic process positive regulation of RNA biosynthetic process regulation of macromolecule biosynthetic process regulation of DNA-templated transcription response to hormone response to endogenous stimulus intracellular signal transduction intracellular signaling cassette regulation of cardiac muscle contraction by calcium ion signaling regulation of cardiac muscle contraction regulation of muscle system process regulation of striated muscle contraction calcium-mediated signaling regulation of muscle contraction negative regulation of potassium ion transport regulation of potassium ion transport potassium ion transport nitric oxide mediated signal transduction positive regulation of cation transmembrane transport sodium ion transmembrane transport regulation of sodium ion transport regulation of sodium ion transmembrane transport positive regulation of sodium ion transport positive regulation of monoatomic ion transport positive regulation of sodium ion transmembrane transport positive regulation of transmembrane transport positive regulation of monoatomic ion transmembrane transport positive regulation of transport sodium ion transport regulation of tube diameter regulation of tube size vascular process in circulatory system blood vessel diameter maintenance vasodilation regulation of anatomical structure size cellular response to endogenous stimulus cellular response to growth factor stimulus response to growth factor monoamine transport import into cell nitrogen compound transport serotonin uptake organic hydroxy compound transport negative regulation of neurotransmitter transport establishment of localization in cell neurotransmitter reuptake regulation of neurotransmitter uptake regulation of neurotransmitter transport regulation of serotonin uptake serotonin transport neurotransmitter transport negative regulation of neurotransmitter uptake negative regulation of serotonin uptake neurotransmitter uptake biological process involved in interspecies interaction between organisms response to lipid response to other organism response to oxygen-containing compound response to external stimulus response to lipopolysaccharide response to biotic stimulus response to bacterium response to external biotic stimulus response to molecule of bacterial origin regulation of blood pressure negative regulation of blood pressure nitric oxide metabolic process nitric oxide biosynthetic process reactive nitrogen species metabolic process	cellular anatomical structure photoreceptor inner segment intracellular anatomical structure cytoplasm cytosol cell periphery sarcolemma plasma membrane membrane intracellular organelle cytoskeleton organelle membraneless organelle intracellular membraneless organelle cellular anatomical structure photoreceptor inner segment intracellular anatomical structure cytoplasm cytosol cell periphery sarcolemma plasma membrane membrane intracellular organelle cytoskeleton organelle membraneless organelle intracellular membraneless organelle neuron spine synapse neuron projection dendritic spine plasma membrane bounded cell projection somatodendritic compartment cell projection postsynapse cell junction dendrite dendritic tree perinuclear region of cytoplasm membrane-bounded organelle intracellular membrane-bounded organelle endomembrane system sarcoplasm endoplasmic reticulum sarcoplasmic reticulum mitochondrion membrane microdomain membrane raft nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen protein-containing complex postsynaptic density neuron to neuron synapse postsynaptic specialization asymmetric synapse

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D	IPR001709	Flavoprotein pyridine nucleotide cytochrome reductase	Domain
A, B, C, D	IPR001433	Oxidoreductase FAD/NAD(P)-binding	Domain
A, B, C, D	IPR001094	Flavodoxin-like	Domain
A, B, C, D	IPR004030	Nitric oxide synthase, N-terminal	Domain
A, B, C, D	IPR023173	NADPH-cytochrome p450 reductase, FAD-binding, alpha-helical domain superfamily	Homologous Superfamily
A, B, C, D	IPR008254	Flavodoxin/nitric oxide synthase	Domain
A, B, C, D	IPR039261	Ferredoxin-NADP reductase (FNR), nucleotide-binding domain	Homologous Superfamily
A, B, C, D	IPR017927	FAD-binding domain, ferredoxin reductase-type	Domain
A, B, C, D	IPR036119	Nitric oxide synthase, N-terminal domain superfamily	Homologous Superfamily
A, B, C, D	IPR044944	Nitric oxide synthase, domain 3 superfamily	Homologous Superfamily
A, B, C, D	IPR044943	Nitric oxide synthase, domain 1 superfamily	Homologous Superfamily
A, B, C, D	IPR003097	Sulfite reductase [NADPH] flavoprotein alpha-component-like, FAD-binding	Domain
A, B, C, D	IPR017938	Riboflavin synthase-like beta-barrel	Homologous Superfamily
A, B, C, D	IPR044940	Nitric oxide synthase, domain 2 superfamily	Homologous Superfamily
A, B, C, D	IPR036034	PDZ superfamily	Homologous Superfamily
A, B, C, D	IPR029039	Flavoprotein-like superfamily	Homologous Superfamily
A, B, C, D	IPR050607	Nitric Oxide Synthase (NOS)	Family
A, B, C, D	IPR012144	Nitric-oxide synthase, eukaryote	Family
A, B, C, D	IPR001478	PDZ domain	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D	Pharos: P29475	hepatic encephalopathy intestinal perforation endogenous depression status epilepticus Radiation Injuries, Experimental alcohol-related birth defect fetal alcohol syndrome nervous system disorder visual epilepsy Parkinson disease schizophrenia melancholia achalasia cerebellar disease fetal alcohol spectrum disorder hepatic encephalopathy intestinal perforation endogenous depression status epilepticus Radiation Injuries, Experimental alcohol-related birth defect fetal alcohol syndrome nervous system disorder visual epilepsy Parkinson disease schizophrenia melancholia achalasia cerebellar disease fetal alcohol spectrum disorder morphine dependence amphetamine abuse hepatic coma ovarian cancer idiopathic achalasia periodontitis large cell medulloblastoma primitive neuroectodermal tumor malignant ependymoma medulloblastoma neurotic disorder atypical teratoid rhabdoid tumor oligodendroglioma colorectal cancer psoriasis malignant glioma erectile dysfunction myopathy nervous system injury astrocytic tumor type 1 diabetes mellitus osteosarcoma partial fetal alcohol syndrome pituitary cancer depressive disorder lung carcinoma psychiatric disorder Duchenne muscular dystrophy glioblastoma chronic liver failure

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.