5EDG

CRYSTAL STRUCTURE OF HUMAN PHOSPHODIESTERASE 10 IN COMPLEX WITH c1(c(nc([nH]1)Cl)c2ccccc2)C4=NN(c3cccc(c3)OC(F)(F)F)C=CC4=O, micromolar IC50=0.029618

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
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	d5edga_	All alpha proteins	HD-domain/PDEase-like	HD-domain/PDEase-like	automated matches	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d5edgc_	All alpha proteins	HD-domain/PDEase-like	HD-domain/PDEase-like	automated matches	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d5edgd1	All alpha proteins	HD-domain/PDEase-like	HD-domain/PDEase-like	automated matches	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d5edgd2	Artifacts	Tags	Tags	Tags	N-terminal Tags	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d5edgb1	All alpha proteins	HD-domain/PDEase-like	HD-domain/PDEase-like	automated matches	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d5edgb2	Artifacts	Tags	Tags	Tags	C-terminal Tags	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	PDEase_I	e5edgA1	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	e5edgC1	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	e5edgD1	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	e5edgB1	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)
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)
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)

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, C, D	cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A	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'-cGMP-stimulated cyclic-nucleotide phosphodiesterase activity binding adenyl ribonucleotide binding cyclic nucleotide binding nucleotide binding purine ribonucleotide binding nucleoside phosphate 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'-cGMP-stimulated cyclic-nucleotide phosphodiesterase activity 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 heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding 3',5'-cyclic-GMP phosphodiesterase activity guanyl nucleotide binding guanyl ribonucleotide binding cGMP binding 3',5'-cyclic-AMP phosphodiesterase activity cation binding metal ion binding	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 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 cellular response to stimulus regulation of cellular process response to stimulus signaling negative regulation of signaling negative regulation of intracellular signal transduction negative regulation of biological process regulation of signal transduction intracellular signal transduction negative regulation of cell communication cell communication regulation of intracellular signal transduction intracellular signaling cassette negative regulation of cellular process signal transduction regulation of cGMP-mediated signaling regulation of biological process regulation of signaling negative regulation of cGMP-mediated signaling negative regulation of response to stimulus cGMP-mediated signaling biological regulation negative regulation of signal transduction regulation of response to stimulus regulation of cell communication cAMP-mediated signaling cAMP catabolic process cAMP metabolic process	cellular anatomical structure intracellular anatomical structure cytoplasm cytosol
B	cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A	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'-cGMP-stimulated cyclic-nucleotide phosphodiesterase activity binding adenyl ribonucleotide binding cyclic nucleotide binding nucleotide binding purine ribonucleotide binding nucleoside phosphate 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'-cGMP-stimulated cyclic-nucleotide phosphodiesterase activity 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 heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding 3',5'-cyclic-GMP phosphodiesterase activity guanyl nucleotide binding guanyl ribonucleotide binding cGMP binding 3',5'-cyclic-AMP phosphodiesterase activity cation binding metal ion binding	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 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 cellular response to stimulus regulation of cellular process response to stimulus signaling negative regulation of signaling negative regulation of intracellular signal transduction negative regulation of biological process regulation of signal transduction intracellular signal transduction negative regulation of cell communication cell communication regulation of intracellular signal transduction intracellular signaling cassette negative regulation of cellular process signal transduction regulation of cGMP-mediated signaling regulation of biological process regulation of signaling negative regulation of cGMP-mediated signaling negative regulation of response to stimulus cGMP-mediated signaling biological regulation negative regulation of signal transduction regulation of response to stimulus regulation of cell communication cAMP-mediated signaling cAMP catabolic process cAMP metabolic process	cellular anatomical structure intracellular anatomical structure cytoplasm cytosol

InterPro: Protein Family Classification InterPro Database Homepage

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

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, C, D	Pharos: Q9Y233	striatal degeneration, autosomal dominant 2 dyskinesia, limb and orofacial, infantile-onset Nonorganic psychosis Pick disease atypical teratoid rhabdoid tumor Hashimoto thyroiditis invasive ductal breast carcinoma malignant ependymoma medulloblastoma oligodendroglioma pilocytic astrocytoma subependymal giant cell astrocytoma astrocytic tumor bipolar disorder cutaneous lupus erythematosus striatal degeneration, autosomal dominant 2 dyskinesia, limb and orofacial, infantile-onset Nonorganic psychosis Pick disease atypical teratoid rhabdoid tumor Hashimoto thyroiditis invasive ductal breast carcinoma malignant ependymoma medulloblastoma oligodendroglioma pilocytic astrocytoma subependymal giant cell astrocytoma astrocytic tumor bipolar disorder cutaneous lupus erythematosus hyperthyroidism large cell medulloblastoma malignant glioma ovarian cancer Sjogren syndrome atrial fibrillation breast cancer hypothyroidism lung carcinoma malignant mesothelioma
B	Pharos: Q9Y233	striatal degeneration, autosomal dominant 2 dyskinesia, limb and orofacial, infantile-onset Nonorganic psychosis Pick disease atypical teratoid rhabdoid tumor Hashimoto thyroiditis invasive ductal breast carcinoma malignant ependymoma medulloblastoma oligodendroglioma pilocytic astrocytoma subependymal giant cell astrocytoma astrocytic tumor bipolar disorder cutaneous lupus erythematosus striatal degeneration, autosomal dominant 2 dyskinesia, limb and orofacial, infantile-onset Nonorganic psychosis Pick disease atypical teratoid rhabdoid tumor Hashimoto thyroiditis invasive ductal breast carcinoma malignant ependymoma medulloblastoma oligodendroglioma pilocytic astrocytoma subependymal giant cell astrocytoma astrocytic tumor bipolar disorder cutaneous lupus erythematosus hyperthyroidism large cell medulloblastoma malignant glioma ovarian cancer Sjogren syndrome atrial fibrillation breast cancer hypothyroidism lung carcinoma malignant mesothelioma

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.