3JWQ

Crystal structure of chimeric PDE5/PDE6 catalytic domain complexed with sildenafil

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	d3jwqa_	All alpha proteins	HD-domain/PDEase-like	HD-domain/PDEase-like	PDEase	automated matches	human (Homo sapiens ) [TaxId: 9606 ], human (Homo sapiens ) [TaxId: 9606 ], human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d3jwqd_	All alpha proteins	HD-domain/PDEase-like	HD-domain/PDEase-like	PDEase	automated matches	human (Homo sapiens ) [TaxId: 9606 ], human (Homo sapiens ) [TaxId: 9606 ], human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d3jwqb_	All alpha proteins	HD-domain/PDEase-like	HD-domain/PDEase-like	PDEase	automated matches	human (Homo sapiens ) [TaxId: 9606 ], human (Homo sapiens ) [TaxId: 9606 ], human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d3jwqc1	All alpha proteins	HD-domain/PDEase-like	HD-domain/PDEase-like	PDEase	automated matches	human (Homo sapiens ) [TaxId: 9606 ], human (Homo sapiens ) [TaxId: 9606 ], human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d3jwqc2	Artifacts	Tags	Tags	Tags	N-terminal Tags	human (Homo sapiens ) [TaxId: 9606 ], human (Homo sapiens ) [TaxId: 9606 ], 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	HD-domain/PDEase-like	8042136	3000943	SCOP2B (2022-06-29)
D	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)
C	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	e3jwqA1	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)
D	PDEase_I	e3jwqD1	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	e3jwqB1	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)
C	PDEase_I	e3jwqC1	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)
D	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)
C	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, C, D	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, C, D	cGMP-specific 3',5'-cyclic phosphodiesterase catalytic domain, Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha chimera	calmodulin-activated 3',5'-cyclic-GMP phosphodiesterase 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 binding cyclic nucleotide binding nucleotide binding guanyl ribonucleotide binding calmodulin-activated 3',5'-cyclic-GMP phosphodiesterase 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 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 calmodulin-activated dual specificity 3',5'-cyclic-GMP, 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 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 multicellular organismal process system process relaxation of cardiac muscle muscle system process relaxation of muscle 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 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 cellular process purine ribonucleotide metabolic process developmental process sexual reproduction cellular developmental process reproductive process multicellular organismal reproductive process oogenesis cell development cellular process involved in reproduction in multicellular organism developmental process involved in reproduction female gamete generation gamete generation oocyte development cell differentiation anatomical structure development germ cell development oocyte differentiation negative regulation of lymphocyte proliferation regulation of cellular process 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 T cell activation lymphocyte proliferation regulation of immune system process regulation of leukocyte proliferation regulation of biological process cell population proliferation negative regulation of T cell activation negative regulation of leukocyte cell-cell adhesion regulation of cell population proliferation mononuclear cell proliferation negative regulation of cell-cell adhesion regulation of leukocyte cell-cell adhesion negative regulation of multicellular organismal process negative regulation of leukocyte activation lymphocyte activation negative regulation of lymphocyte activation leukocyte proliferation leukocyte cell-cell adhesion leukocyte activation negative regulation of mononuclear cell proliferation cell adhesion cell-cell adhesion negative regulation of cellular process regulation of multicellular organismal process regulation of cell-cell adhesion T cell proliferation regulation of lymphocyte proliferation negative regulation of cell population proliferation regulation of cell adhesion biological regulation cell activation regulation of T cell activation negative regulation of cell activation regulation of T cell proliferation negative regulation of immune system process immune system process regulation of mononuclear cell proliferation regulation of lymphocyte activation cellular response to stimulus positive regulation of cell communication positive regulation of signal transduction response to stimulus positive regulation of phosphorylation regulation of catalytic activity regulation of signal transduction regulation of transferase activity positive regulation of phosphate metabolic process regulation of MAP kinase activity intracellular signal transduction regulation of primary metabolic process cell communication positive regulation of protein serine/threonine kinase activity positive regulation of metabolic process regulation of phosphate metabolic process intracellular signaling cassette positive regulation of macromolecule metabolic process signal transduction protein modification process positive regulation of protein phosphorylation positive regulation of MAP kinase activity protein phosphorylation positive regulation of phosphorus metabolic process phosphorylation positive regulation of MAPK cascade regulation of protein metabolic process positive regulation of intracellular signal transduction regulation of MAPK cascade regulation of molecular function positive regulation of kinase activity regulation of kinase activity regulation of response to stimulus regulation of protein serine/threonine kinase activity macromolecule modification regulation of phosphorus metabolic process macromolecule metabolic process regulation of metabolic process regulation of protein modification process regulation of protein phosphorylation signaling positive regulation of protein metabolic process positive regulation of biological process positive regulation of response to stimulus positive regulation of molecular function positive regulation of protein modification process regulation of intracellular signal transduction protein metabolic process positive regulation of protein kinase activity positive regulation of cellular process regulation of signaling positive regulation of transferase activity positive regulation of catalytic activity regulation of protein kinase activity regulation of macromolecule metabolic process MAPK cascade regulation of cell communication regulation of phosphorylation positive regulation of signaling regulation of developmental process regulation of reproductive process regulation of oogenesis regulation of cell differentiation regulation of cell development positive regulation of developmental process positive regulation of cell differentiation positive regulation of oocyte development positive regulation of reproductive process regulation of oocyte development positive regulation of cell development muscle hypertrophy regulation of muscle adaptation positive regulation of cardiac muscle hypertrophy regulation of system process striated muscle hypertrophy regulation of 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 nitric oxide mediated signal transduction regulation of nitric oxide mediated signal transduction cAMP-mediated signaling 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	cellular anatomical structure intracellular anatomical structure cytoplasm cytosol cell periphery plasma membrane membrane

InterPro: Protein Family Classification InterPro Database Homepage

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

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D	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

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.