3JWR

Crystal structure of chimeric PDE5/PDE6 catalytic domain complexed with 3-isobutyl-1-methylxanthine (IBMX) and PDE6 gamma-subunit inhibitory peptide 70-87.

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	d3jwrb1	All alpha proteins	HD-domain/PDEase-like	HD-domain/PDEase-like	PDEase	automated matches	(Homo sapiens ) [TaxId: 9606 ], (Homo sapiens ) [TaxId: 9606 ], (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d3jwrb2	Artifacts	Tags	Tags	Tags	N-terminal Tags	(Homo sapiens ) [TaxId: 9606 ], (Homo sapiens ) [TaxId: 9606 ], (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	HD-domain/PDEase-like	8042136	3000943	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	HD-domain/PDEase-like	8042136	3000943	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	PDEase_I	e3jwrA1	A: alpha complex topology	X: PDEase-like	H: HD-domain/PDEase-like (From Topology)	T: HD-domain/PDEase-like	F: PDEase_I	ECOD (1.6)
B	PDEase_I	e3jwrB1	A: alpha complex topology	X: PDEase-like	H: HD-domain/PDEase-like (From Topology)	T: HD-domain/PDEase-like	F: PDEase_I	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	1.10.1300.10	Mainly Alpha	Orthogonal Bundle	Catalytic domain of cyclic nucleotide phosphodiesterase 4b2b	3'5'-cyclic nucleotide phosphodiesterase, catalytic domain	CATH (4.3.0)
B	1.10.1300.10	Mainly Alpha	Orthogonal Bundle	Catalytic domain of cyclic nucleotide phosphodiesterase 4b2b	3'5'-cyclic nucleotide phosphodiesterase, catalytic domain	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF00233	3'5'-cyclic nucleotide phosphodiesterase (PDEase_I)	3'5'-cyclic nucleotide phosphodiesterase	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	cGMP-specific 3',5'-cyclic phosphodiesterase catalytic domain, Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha chimera	phosphoric ester hydrolase activity hydrolase activity, acting on ester bonds phosphoric diester hydrolase activity 3',5'-cyclic-nucleotide phosphodiesterase activity hydrolase activity cyclic-nucleotide phosphodiesterase activity catalytic activity 3',5'-cyclic-GMP phosphodiesterase activity guanyl nucleotide binding binding cyclic nucleotide binding nucleotide binding guanyl ribonucleotide binding purine ribonucleotide binding phosphoric ester hydrolase activity hydrolase activity, acting on ester bonds phosphoric diester hydrolase activity 3',5'-cyclic-nucleotide phosphodiesterase activity hydrolase activity cyclic-nucleotide phosphodiesterase activity catalytic activity 3',5'-cyclic-GMP phosphodiesterase activity guanyl nucleotide binding binding cyclic nucleotide binding nucleotide binding guanyl ribonucleotide binding purine ribonucleotide binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding cGMP binding small molecule binding 3',5'-cyclic-AMP phosphodiesterase activity cation binding metal ion binding	multicellular organismal process system process relaxation of cardiac muscle muscle system process relaxation of muscle cell population proliferation cell activation lymphocyte activation leukocyte proliferation leukocyte activation immune system process mononuclear cell proliferation T cell activation lymphocyte proliferation multicellular organismal process system process relaxation of cardiac muscle muscle system process relaxation of muscle cell population proliferation cell activation lymphocyte activation leukocyte proliferation leukocyte activation immune system process mononuclear cell proliferation T cell activation lymphocyte proliferation cellular process T cell proliferation ribose phosphate metabolic process ribonucleotide catabolic process catabolic process carbohydrate derivative metabolic process organophosphate catabolic process nucleoside phosphate catabolic process cyclic nucleotide metabolic process nucleobase-containing compound metabolic process purine nucleotide metabolic process ribonucleotide metabolic process nucleobase-containing small molecule metabolic process phosphate-containing compound metabolic process small molecule metabolic process purine ribonucleotide catabolic process phosphorus metabolic process nucleotide catabolic process nucleoside phosphate metabolic process purine nucleotide catabolic process carbohydrate derivative catabolic process cyclic purine nucleotide metabolic process cellular metabolic process primary metabolic process purine-containing compound catabolic process cyclic nucleotide catabolic process nucleotide metabolic process purine-containing compound metabolic process nucleobase-containing compound catabolic process cGMP metabolic process organophosphate metabolic process cGMP catabolic process metabolic process purine ribonucleotide metabolic process regulation of cellular process sexual reproduction cellular developmental process regulation of developmental process regulation of reproductive process regulation of oogenesis reproductive process positive regulation of biological process cell development cellular process involved in reproduction in multicellular organism regulation of cell differentiation developmental process involved in reproduction female gamete generation gamete generation regulation of cell development oocyte development positive regulation of developmental process positive regulation of cell differentiation cell differentiation positive regulation of oocyte development anatomical structure development regulation of multicellular organismal process positive regulation of cellular process positive regulation of reproductive process developmental process regulation of biological process regulation of oocyte development multicellular organismal reproductive process oogenesis positive regulation of cell development biological regulation germ cell development oocyte differentiation muscle hypertrophy regulation of muscle adaptation positive regulation of cardiac muscle hypertrophy response to stimulus regulation of system process striated muscle hypertrophy regulation of muscle system process regulation of cardiac muscle hypertrophy regulation of muscle hypertrophy muscle adaptation regulation of response to stimulus positive regulation of muscle hypertrophy cardiac muscle hypertrophy positive regulation of multicellular organismal process cellular response to stimulus nitric oxide mediated signal transduction regulation of signaling regulation of nitric oxide mediated signal transduction signaling regulation of signal transduction intracellular signal transduction cell communication regulation of intracellular signal transduction intracellular signaling cassette regulation of cell communication signal transduction cAMP-mediated signaling negative regulation of lymphocyte proliferation regulation of leukocyte activation negative regulation of biological process regulation of cell activation negative regulation of T cell proliferation negative regulation of cell adhesion negative regulation of leukocyte proliferation regulation of immune system process regulation of leukocyte proliferation negative regulation of T cell activation negative regulation of leukocyte cell-cell adhesion regulation of cell population proliferation negative regulation of cell-cell adhesion regulation of leukocyte cell-cell adhesion negative regulation of multicellular organismal process negative regulation of leukocyte activation negative regulation of lymphocyte activation leukocyte cell-cell adhesion negative regulation of mononuclear cell proliferation cell adhesion cell-cell adhesion negative regulation of cellular process regulation of cell-cell adhesion regulation of lymphocyte proliferation negative regulation of cell population proliferation regulation of cell adhesion regulation of T cell activation negative regulation of cell activation regulation of T cell proliferation negative regulation of immune system process regulation of mononuclear cell proliferation regulation of lymphocyte activation heart process regulation of heart contraction cardiac muscle contraction striated muscle contraction negative regulation of muscle contraction circulatory system process negative regulation of cardiac muscle contraction blood circulation negative regulation of blood circulation regulation of cardiac muscle contraction muscle contraction negative regulation of heart contraction regulation of blood circulation regulation of striated muscle contraction regulation of muscle contraction heart contraction negative regulation of striated muscle contraction detection of light stimulus response to light stimulus phototransduction detection of external stimulus detection of visible light response to external stimulus detection of abiotic stimulus detection of stimulus response to abiotic stimulus response to radiation phototransduction, visible light sensory perception of light stimulus sensory perception nervous system process visual perception sensory organ development photoreceptor cell differentiation visual system development retina development in camera-type eye neural retina development eye morphogenesis multicellular organism development neurogenesis neuron differentiation retinal cone cell differentiation eye photoreceptor cell differentiation animal organ morphogenesis sensory system development system development photoreceptor cell development camera-type eye morphogenesis eye development eye photoreceptor cell development animal organ development retinal cone cell development nervous system development camera-type eye photoreceptor cell differentiation generation of neurons retina morphogenesis in camera-type eye anatomical structure morphogenesis sensory organ morphogenesis neuron development camera-type eye development	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol cell periphery plasma membrane membrane
C, D	Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma	cytoskeletal protein binding spectrin binding protein-containing complex binding protein binding binding enzyme regulator activity molecular function inhibitor activity molecular function regulator activity enzyme inhibitor activity phosphoric ester hydrolase activity hydrolase activity, acting on ester bonds phosphoric diester hydrolase activity 3',5'-cyclic-nucleotide phosphodiesterase activity hydrolase activity cytoskeletal protein binding spectrin binding protein-containing complex binding protein binding binding enzyme regulator activity molecular function inhibitor activity molecular function regulator activity enzyme inhibitor activity phosphoric ester hydrolase activity hydrolase activity, acting on ester bonds phosphoric diester hydrolase activity 3',5'-cyclic-nucleotide phosphodiesterase activity hydrolase activity cyclic-nucleotide phosphodiesterase activity catalytic activity 3',5'-cyclic-GMP phosphodiesterase activity guanyl nucleotide binding cyclic nucleotide binding nucleotide binding guanyl ribonucleotide binding purine ribonucleotide binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding cGMP binding small molecule binding	cellular response to stimulus positive regulation of cell communication regulation of biological process regulation of signaling regulation of cellular process positive regulation of signal transduction response to stimulus signaling biological regulation positive regulation of biological process regulation of signal transduction positive regulation of G protein-coupled receptor signaling pathway cell communication positive regulation of response to stimulus regulation of response to stimulus cellular response to stimulus positive regulation of cell communication regulation of biological process regulation of signaling regulation of cellular process positive regulation of signal transduction response to stimulus signaling biological regulation positive regulation of biological process regulation of signal transduction positive regulation of G protein-coupled receptor signaling pathway cell communication positive regulation of response to stimulus regulation of response to stimulus regulation of cell communication G protein-coupled receptor signaling pathway cellular process signal transduction regulation of G protein-coupled receptor signaling pathway positive regulation of cellular process positive regulation of signaling intracellular signal transduction regulation of intracellular signal transduction intracellular signaling cassette positive regulation of MAPK cascade positive regulation of intracellular signal transduction regulation of MAPK cascade MAPK cascade multicellular organismal process sensory perception of light stimulus system process sensory perception nervous system process visual perception cell surface receptor protein tyrosine kinase signaling pathway positive regulation of ERBB signaling pathway regulation of epidermal growth factor receptor signaling pathway epidermal growth factor receptor signaling pathway enzyme-linked receptor protein signaling pathway positive regulation of epidermal growth factor receptor signaling pathway regulation of ERBB signaling pathway cell surface receptor signaling pathway ERBB signaling pathway	membrane-bounded organelle non-motile cilium membrane plasma membrane cilium 9+0 non-motile cilium neuron projection cellular anatomical entity ciliary membrane photoreceptor outer segment membrane photoreceptor outer segment plasma membrane bounded cell projection cell periphery cell projection membrane-bounded organelle non-motile cilium membrane plasma membrane cilium 9+0 non-motile cilium neuron projection cellular anatomical entity ciliary membrane photoreceptor outer segment membrane photoreceptor outer segment plasma membrane bounded cell projection cell periphery cell projection bounding membrane of organelle photoreceptor cell cilium organelle plasma membrane region organelle membrane cell projection membrane photoreceptor disc membrane

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR003607	HD/PDEase domain	Domain
A, B	IPR002073	3'5'-cyclic nucleotide phosphodiesterase, catalytic domain	Domain
A, B	IPR036971	3'5'-cyclic nucleotide phosphodiesterase, catalytic domain superfamily	Homologous Superfamily
A, B	IPR003018	GAF domain	Domain
A, B	IPR029016	GAF-like domain superfamily	Homologous Superfamily
A, B	IPR023088	3'5'-cyclic nucleotide phosphodiesterase	Family
A, B	IPR023174	3'5'-cyclic nucleotide phosphodiesterase, conserved site	Conserved Site
A, B	IPR003607	HD/PDEase domain	Domain
A, B	IPR002073	3'5'-cyclic nucleotide phosphodiesterase, catalytic domain	Domain
A, B	IPR036971	3'5'-cyclic nucleotide phosphodiesterase, catalytic domain superfamily	Homologous Superfamily
A, B	IPR003018	GAF domain	Domain
A, B	IPR029016	GAF-like domain superfamily	Homologous Superfamily
A, B	IPR023088	3'5'-cyclic nucleotide phosphodiesterase	Family
A, B	IPR023174	3'5'-cyclic nucleotide phosphodiesterase, conserved site	Conserved Site
C, D	IPR006952	Retinal cGMP phosphodiesterase, gamma subunit	Family
C, D	IPR037030	Retinal cGMP phosphodiesterase, gamma subunit superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: P51160	Neoplasm Metastasis erectile dysfunction malignant pancreatic neoplasm ovarian cancer pituitary cancer atrial fibrillation breast cancer pulmonary hypertension congestive heart failure exocrine pancreatic carcinoma head and neck cancer lung adenocarcinoma malignant ependymoma medulloblastoma non-small cell lung carcinoma Neoplasm Metastasis erectile dysfunction malignant pancreatic neoplasm ovarian cancer pituitary cancer atrial fibrillation breast cancer pulmonary hypertension congestive heart failure exocrine pancreatic carcinoma head and neck cancer lung adenocarcinoma malignant ependymoma medulloblastoma non-small cell lung carcinoma peripheral vascular disease atypical teratoid rhabdoid tumor priapism breast carcinoma type 2 diabetes mellitus diabetes mellitus gastric cancer hypertensive disorder lung cancer malignant mesothelioma osteosarcoma Peyronie disease premature ejaculation benign prostatic hyperplasia pulmonary arterial hypertension ulcerative colitis gastric carcinoma large cell medulloblastoma malignant colon neoplasm achromatopsia cone dystrophy 4 cone dystrophy amphetamine abuse Amphetamine Addiction cone-rod dystrophy atrial fibrillation
C, D	Pharos: P18545	retinitis pigmentosa retinitis pigmentosa 57 age-related macular degeneration cone-rod dystrophy large cell medulloblastoma Prevention of Cerebral Thrombosis atrial fibrillation corneal disease psoriasis intellectual disability retinal degeneration wet macular degeneration

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.