1PTW

The Crystal Structure of AMP-Bound PDE4 Suggests a Mechanism for Phosphodiesterase Catalysis

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	d1ptwb_	All alpha proteins	HD-domain/PDEase-like	HD-domain/PDEase-like	PDEase	Catalytic domain of cyclic nucleotide phosphodiesterase pde4d	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d1ptwa_	All alpha proteins	HD-domain/PDEase-like	HD-domain/PDEase-like	PDEase	Catalytic domain of cyclic nucleotide phosphodiesterase pde4d	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d1ptwc_	All alpha proteins	HD-domain/PDEase-like	HD-domain/PDEase-like	PDEase	Catalytic domain of cyclic nucleotide phosphodiesterase pde4d	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d1ptwd_	All alpha proteins	HD-domain/PDEase-like	HD-domain/PDEase-like	PDEase	Catalytic domain of cyclic nucleotide phosphodiesterase pde4d	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	HD-domain/PDEase-like	8034051	3000943	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	HD-domain/PDEase-like	8034051	3000943	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	HD-domain/PDEase-like	8034051	3000943	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	HD-domain/PDEase-like	8034051	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)
B	PDEase_I	e1ptwB1	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)
A	PDEase_I	e1ptwA1	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	e1ptwC1	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	e1ptwD1	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)
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)
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)
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)
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)

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	cAMP-specific phosphodiesterase PDE4D2	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 beta-2 adrenergic receptor binding protein binding binding adrenergic receptor binding signaling receptor binding G protein-coupled receptor binding scaffold protein 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 beta-2 adrenergic receptor binding protein binding binding adrenergic receptor binding signaling receptor binding G protein-coupled receptor binding scaffold protein binding 3',5'-cyclic-AMP phosphodiesterase activity channel regulator activity ion channel regulator activity calcium channel regulator activity molecular function regulator activity transporter regulator activity transmembrane transporter binding heterocyclic compound binding small molecule binding adenyl ribonucleotide binding cyclic nucleotide binding nucleotide binding purine ribonucleotide binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding cAMP binding adenyl nucleotide binding carbohydrate derivative binding ribonucleotide binding signaling receptor regulator activity 3',5'-cyclic-GMP phosphodiesterase activity enzyme binding cation binding metal ion binding ATPase binding	heart process multicellular organismal process system process regulation of actin filament-based process regulation of cellular process regulation of heart contraction regulation of system process cardiac muscle contraction striated muscle contraction circulatory system process actin filament-based process regulation of multicellular organismal process blood circulation cardiac muscle cell contraction heart process multicellular organismal process system process regulation of actin filament-based process regulation of cellular process regulation of heart contraction regulation of system process cardiac muscle contraction striated muscle contraction circulatory system process actin filament-based process regulation of multicellular organismal process blood circulation cardiac muscle cell contraction regulation of biological process biological regulation regulation of cardiac muscle contraction actin filament-based movement muscle contraction muscle system process regulation of muscle system process regulation of blood circulation regulation of striated muscle contraction regulation of actin filament-based movement regulation of muscle contraction regulation of cardiac muscle cell contraction cellular process actin-mediated cell contraction heart contraction positive regulation of biological process positive regulation of heart rate positive regulation of blood circulation positive regulation of heart contraction positive regulation of multicellular organismal process regulation of biological quality regulation of heart rate cellular biosynthetic process positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process regulation of interleukin-5 production positive regulation of biosynthetic process regulation of cytokine production cytokine production positive regulation of macromolecule metabolic process interleukin-5 production positive regulation of cellular process regulation of biosynthetic process cellular metabolic process regulation of cellular metabolic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of cellular biosynthetic process regulation of gene expression biosynthetic process positive regulation of gene expression regulation of macromolecule biosynthetic process metabolic process macromolecule metabolic process positive regulation of cytokine production regulation of metabolic process positive regulation of interleukin-5 production positive regulation of cellular biosynthetic process cellular response to stimulus immune response-regulating cell surface receptor signaling pathway response to stimulus signaling cell communication positive regulation of response to stimulus immune response-activating signaling pathway immune response-regulating signaling pathway positive regulation of immune response regulation of immune system process signal transduction positive regulation of immune system process cell surface receptor signaling pathway immune response-activating cell surface receptor signaling pathway immune response T cell receptor signaling pathway regulation of response to stimulus immune system process regulation of immune response antigen receptor-mediated signaling pathway activation of immune response regulation of calcium ion transport regulation of localization intracellular calcium ion homeostasis negative regulation of biological process sarcoplasmic reticulum calcium ion transport release of sequestered calcium ion into cytosol by sarcoplasmic reticulum calcium ion transport localization monoatomic cation homeostasis monoatomic cation transport intracellular monoatomic ion homeostasis release of sequestered calcium ion into cytosol by endoplasmic reticulum regulation of release of sequestered calcium ion into cytosol regulation of monoatomic ion transport inorganic ion transmembrane transport establishment of localization inorganic cation transmembrane transport maintenance of location transmembrane transport release of sequestered calcium ion into cytosol regulation of transmembrane transport chemical homeostasis cellular localization inorganic ion homeostasis transport homeostatic process monoatomic ion transmembrane transport calcium ion homeostasis regulation of monoatomic ion transmembrane transport negative regulation of sequestering of calcium ion metal ion transport maintenance of location in cell regulation of calcium ion transmembrane transport monoatomic cation transmembrane transport intracellular monoatomic cation homeostasis monoatomic ion homeostasis negative regulation of cellular process monoatomic ion transport intracellular chemical homeostasis regulation of metal ion transport regulation of sequestering of calcium ion calcium ion transmembrane import into cytosol regulation of transport sequestering of calcium ion cellular homeostasis regulation of monoatomic cation transmembrane transport calcium ion transmembrane transport regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum negative regulation of blood circulation negative regulation of heart contraction negative regulation of multicellular organismal process regulation of protein modification process regulation of protein phosphorylation negative regulation of phosphate metabolic process regulation of peptidyl-serine phosphorylation negative regulation of cellular metabolic process peptidyl-serine modification regulation of primary metabolic process peptidyl-serine phosphorylation regulation of phosphate metabolic process phosphate-containing compound metabolic process negative regulation of protein modification process peptidyl-amino acid modification protein metabolic process protein modification process phosphorus metabolic process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process negative regulation of peptidyl-serine phosphorylation protein phosphorylation phosphorylation regulation of protein metabolic process negative regulation of metabolic process primary metabolic process negative regulation of protein phosphorylation macromolecule modification negative regulation of phosphorus metabolic process regulation of phosphorylation regulation of phosphorus metabolic process negative regulation of phosphorylation cellular response to nitrogen compound response to organophosphorus cellular response to organic cyclic compound response to oxygen-containing compound response to nitrogen compound response to purine-containing compound response to cAMP cellular response to oxygen-containing compound cellular response to chemical stimulus response to chemical cellular response to cAMP response to organic cyclic compound cell communication by electrical coupling involved in cardiac conduction cell communication by electrical coupling regulation of cell communication by electrical coupling involved in cardiac conduction cardiac conduction regulation of cell communication cell communication involved in cardiac conduction regulation of cell communication by electrical coupling response to epinephrine cellular response to epinephrine stimulus adrenergic receptor signaling pathway G protein-coupled receptor signaling pathway developmental process epithelium development endothelial cell differentiation cellular developmental process endothelium development cell development tissue development epithelial cell differentiation endothelial cell development epithelial cell development cell differentiation establishment of endothelial barrier anatomical structure development regulation of interleukin-2 production interleukin-2 production positive regulation of interleukin-2 production negative regulation of signaling regulation of signal transduction negative regulation of G protein-coupled receptor signaling pathway negative regulation of cell communication regulation of G protein-coupled receptor signaling pathway regulation of signaling negative regulation of response to stimulus adenylate cyclase-activating G protein-coupled receptor signaling pathway negative regulation of signal transduction negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway adenylate cyclase-modulating G protein-coupled receptor signaling pathway regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway intracellular signal transduction cAMP-mediated signaling intracellular signaling cassette regulation of calcium ion transmembrane transport via high voltage-gated calcium channel calcium ion transmembrane transport via high voltage-gated calcium channel negative regulation of relaxation of muscle relaxation of cardiac muscle regulation of relaxation of cardiac muscle relaxation of muscle negative regulation of relaxation of cardiac muscle regulation of 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 small molecule metabolic process purine ribonucleotide catabolic process nucleotide catabolic process nucleoside phosphate metabolic process cAMP catabolic process purine nucleotide catabolic process carbohydrate derivative catabolic process cAMP metabolic process cyclic purine nucleotide metabolic process purine-containing compound catabolic process cyclic nucleotide catabolic process nucleotide metabolic process purine-containing compound metabolic process nucleobase-containing compound catabolic process organophosphate metabolic process purine ribonucleotide metabolic process regulation of type II interferon production type II interferon production positive regulation of type II interferon production	membrane cellular anatomical entity cell periphery apical part of cell plasma membrane plasma membrane region apical plasma membrane intracellular organelle centrosome microtubule organizing center intracellular anatomical structure cytoskeleton organelle intracellular non-membrane-bounded organelle membrane cellular anatomical entity cell periphery apical part of cell plasma membrane plasma membrane region apical plasma membrane intracellular organelle centrosome microtubule organizing center intracellular anatomical structure cytoskeleton organelle intracellular non-membrane-bounded organelle microtubule cytoskeleton non-membrane-bounded organelle cytoplasm cytosol protein-containing complex transmembrane transporter complex membrane protein complex cation channel complex transporter complex calcium channel complex monoatomic ion channel complex perinuclear region of cytoplasm plasma membrane protein complex voltage-gated calcium channel complex membrane-bounded organelle nucleus intracellular membrane-bounded organelle

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	IPR023174	3'5'-cyclic nucleotide phosphodiesterase, conserved site	Conserved Site
A, B, C, D	IPR002073	3'5'-cyclic nucleotide phosphodiesterase, catalytic domain	Domain
A, B, C, D	IPR040844	Phosphodiesterase 4 upstream conserved regions (UCR)	Domain
A, B, C, D	IPR023088	3'5'-cyclic nucleotide phosphodiesterase	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D	Pharos: Q08499	acrodysostosis acrodysostosis 2 with or without hormone resistance amphetamine abuse prostate cancer chromosome 5q12 deletion syndrome asthma Crohn disease tuberculosis Urinary incontinence esophageal squamous cell carcinoma hepatocellular carcinoma interstitial lung disease malignant colon neoplasm acrodysostosis with multiple hormone resistance pancreatic intraductal papillary-mucinous carcinoma acrodysostosis acrodysostosis 2 with or without hormone resistance amphetamine abuse prostate cancer chromosome 5q12 deletion syndrome asthma Crohn disease tuberculosis Urinary incontinence esophageal squamous cell carcinoma hepatocellular carcinoma interstitial lung disease malignant colon neoplasm acrodysostosis with multiple hormone resistance pancreatic intraductal papillary-mucinous carcinoma aphthous stomatitis pilocytic astrocytoma atopic eczema breast carcinoma psoriatic arthritis Sjogren syndrome ulcerative colitis depressive disorder exocrine pancreatic carcinoma large cell medulloblastoma acrodysostosis 1 with or without hormone resistance malignant glioma pancreatic intraductal papillary-mucinous neoplasm atypical teratoid rhabdoid tumor carcinoma of esophagus schizophrenia glioblastoma intellectual disability lung cancer malignant pancreatic neoplasm adrenal cortex carcinoma non-small cell lung carcinoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia astrocytic tumor primitive neuroectodermal tumor psoriasis

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.