4CBY

Design, synthesis, and biological evaluation of potent and selective Class IIa HDAC inhibitors as a potential therapy for Huntington's disease

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	d4cbyb_	Alpha and beta proteins (a/b)	Arginase/deacetylase	Arginase/deacetylase	Histone deacetylase, HDAC	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d4cbya_	Alpha and beta proteins (a/b)	Arginase/deacetylase	Arginase/deacetylase	Histone deacetylase, HDAC	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d4cbyc_	Alpha and beta proteins (a/b)	Arginase/deacetylase	Arginase/deacetylase	Histone deacetylase, HDAC	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d4cbyd1	Alpha and beta proteins (a/b)	Arginase/deacetylase	Arginase/deacetylase	Histone deacetylase, HDAC	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d4cbyd2	Artifacts	Tags	Tags	Tags	C-terminal Tags	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	Arginase/deacetylase-like	8087563	3000260	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Arginase/deacetylase-like	8087563	3000260	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Arginase/deacetylase-like	8087563	3000260	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Arginase/deacetylase-like	8087563	3000260	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	Hist_deacetyl	e4cbyB1	A: a/b three-layered sandwiches	X: HAD domain-like	H: HAD domain-related	T: Arginase/deacetylase	F: Hist_deacetyl	ECOD (1.6)
A	Hist_deacetyl	e4cbyA1	A: a/b three-layered sandwiches	X: HAD domain-like	H: HAD domain-related	T: Arginase/deacetylase	F: Hist_deacetyl	ECOD (1.6)
C	Hist_deacetyl	e4cbyC1	A: a/b three-layered sandwiches	X: HAD domain-like	H: HAD domain-related	T: Arginase/deacetylase	F: Hist_deacetyl	ECOD (1.6)
D	Hist_deacetyl	e4cbyD1	A: a/b three-layered sandwiches	X: HAD domain-like	H: HAD domain-related	T: Arginase/deacetylase	F: Hist_deacetyl	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
B	3.40.800.20	Alpha Beta	3-Layer(aba) Sandwich	Arginase	Chain A	CATH (4.3.0)
A	3.40.800.20	Alpha Beta	3-Layer(aba) Sandwich	Arginase	Chain A	CATH (4.3.0)
C	3.40.800.20	Alpha Beta	3-Layer(aba) Sandwich	Arginase	Chain A	CATH (4.3.0)
D	3.40.800.20	Alpha Beta	3-Layer(aba) Sandwich	Arginase	Chain A	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D	PF00850	Histone deacetylase domain (Hist_deacetyl)	Histone deacetylase domain	Histones can be reversibly acetylated on several lysine residues. Regulation of transcription is caused in part by this mechanism. Histone deacetylases catalyse the removal of the acetyl group. Histone deacetylases are related to other proteins [1]. ...	Histones can be reversibly acetylated on several lysine residues. Regulation of transcription is caused in part by this mechanism. Histone deacetylases catalyse the removal of the acetyl group. Histone deacetylases are related to other proteins [1].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D	HISTONE DEACETYLASE 4	histone deacetylase binding protein binding binding enzyme binding deacetylase activity protein lysine deacetylase activity catalytic activity, acting on a protein deacylase activity catalytic activity aminoacyltransferase activity ubiquitin-like protein transferase activity acyltransferase activity SUMO transferase activity transferase activity histone deacetylase binding protein binding binding enzyme binding deacetylase activity protein lysine deacetylase activity catalytic activity, acting on a protein deacylase activity catalytic activity aminoacyltransferase activity ubiquitin-like protein transferase activity acyltransferase activity SUMO transferase activity transferase activity molecular adaptor activity histone deacetylase activity identical protein binding cation binding ion binding potassium ion binding alkali metal ion binding metal ion binding small molecule binding transcription factor binding RNA polymerase II-specific DNA-binding transcription factor binding DNA-binding transcription factor binding DNA binding sequence-specific DNA binding double-stranded DNA binding nucleic acid binding RNA polymerase II transcription regulatory region sequence-specific DNA binding cis-regulatory region sequence-specific DNA binding sequence-specific double-stranded DNA binding transcription cis-regulatory region binding organic cyclic compound binding transcription regulatory region nucleic acid binding RNA polymerase II cis-regulatory region sequence-specific DNA binding transition metal ion binding zinc ion binding	peptidyl-lysine deacetylation peptidyl-lysine modification primary metabolic process macromolecule deacylation protein deacetylation protein deacylation macromolecule modification peptidyl-amino acid modification metabolic process cellular process protein metabolic process macromolecule metabolic process protein modification process ribonucleotide catabolic process peptidyl-lysine deacetylation peptidyl-lysine modification primary metabolic process macromolecule deacylation protein deacetylation protein deacylation macromolecule modification peptidyl-amino acid modification metabolic process cellular process protein metabolic process macromolecule metabolic process protein modification process ribonucleotide catabolic process pyridine nucleotide catabolic process regulation of cellular process negative regulation of small molecule metabolic process negative regulation of glycolytic process oxoacid metabolic process negative regulation of biological process carbohydrate catabolic process organophosphate catabolic process carbohydrate derivative metabolic process regulation of generation of precursor metabolites and energy nucleoside phosphate catabolic process organic acid metabolic process negative regulation of ATP metabolic process regulation of primary metabolic process regulation of ATP metabolic process nucleobase-containing compound metabolic process regulation of purine nucleotide catabolic process negative regulation of nucleotide metabolic process regulation of small molecule metabolic process glycolytic process regulation of nucleotide metabolic process regulation of phosphate metabolic process phosphate-containing compound metabolic process pyridine-containing compound metabolic process small molecule metabolic process negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process purine ribonucleotide catabolic process phosphorus metabolic process pyridine nucleotide metabolic process negative regulation of carbohydrate metabolic process nucleoside phosphate metabolic process nicotinamide nucleotide metabolic process pyruvate metabolic process regulation of carbohydrate catabolic process regulation of biological process negative regulation of metabolic process negative regulation of purine nucleotide catabolic process purine nucleoside diphosphate metabolic process purine-containing compound catabolic process nucleotide metabolic process regulation of purine nucleotide metabolic process nucleobase-containing compound catabolic process nucleoside diphosphate metabolic process purine nucleoside diphosphate catabolic process nucleoside diphosphate catabolic process regulation of nucleotide catabolic process regulation of phosphorus metabolic process nucleoside triphosphate metabolic process monocarboxylic acid metabolic process purine ribonucleotide metabolic process regulation of metabolic process pyridine-containing compound catabolic process ribose phosphate metabolic process catabolic process ATP metabolic process negative regulation of purine nucleotide metabolic process negative regulation of phosphate metabolic process purine nucleotide metabolic process ribonucleotide metabolic process nucleobase-containing small molecule metabolic process purine ribonucleoside triphosphate metabolic process negative regulation of cellular process ribonucleoside diphosphate metabolic process ribonucleoside diphosphate catabolic process regulation of carbohydrate metabolic process nucleotide catabolic process ribonucleoside triphosphate metabolic process negative regulation of nucleotide catabolic process negative regulation of catabolic process purine nucleoside triphosphate metabolic process purine nucleotide catabolic process carbohydrate metabolic process carbohydrate derivative catabolic process biological regulation ADP catabolic process carboxylic acid metabolic process regulation of catabolic process generation of precursor metabolites and energy regulation of glycolytic process purine-containing compound metabolic process ADP metabolic process organophosphate metabolic process negative regulation of phosphorus metabolic process purine ribonucleoside diphosphate metabolic process purine ribonucleoside diphosphate catabolic process positive regulation of DNA-binding transcription factor activity RNA metabolic process RNA biosynthetic process positive regulation of molecular function nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process regulation of RNA biosynthetic process regulation of biosynthetic process regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of molecular function regulation of gene expression biosynthetic process regulation of DNA-binding transcription factor activity regulation of macromolecule biosynthetic process regulation of DNA-templated transcription multicellular organismal process immune system process B cell activation cell activation lymphocyte activation leukocyte activation protein sumoylation post-translational protein modification protein modification by small protein conjugation protein modification by small protein conjugation or removal developmental process multicellular organism development anatomical structure development nervous system development system development negative regulation of RNA biosynthetic process transcription by RNA polymerase II negative regulation of macromolecule metabolic process regulation of transcription by RNA polymerase II negative regulation of DNA-templated transcription negative regulation of transcription by RNA polymerase II negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process negative regulation of RNA metabolic process regulation of muscle adaptation system process response to stimulus regulation of system process regulation of muscle system process muscle system process response to muscle inactivity response to stimulus involved in regulation of muscle adaptation muscle adaptation response to denervation involved in regulation of muscle adaptation regulation of response to stimulus response to muscle inactivity involved in regulation of muscle adaptation response to inactivity regulation of multicellular organismal process positive regulation of DNA-templated transcription positive regulation of biological process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of biosynthetic process positive regulation of macromolecule metabolic process positive regulation of cellular process positive regulation of nucleobase-containing compound metabolic process positive regulation of transcription by RNA polymerase II positive regulation of RNA metabolic process positive regulation of RNA biosynthetic process cellular response to stimulus biological process involved in interspecies interaction between organisms signaling response to cytokine cytokine-mediated signaling pathway response to biotic stimulus cell communication interferon-mediated signaling pathway cellular response to type I interferon response to stress innate immune response cellular response to cytokine stimulus signal transduction response to external biotic stimulus cell surface receptor signaling pathway immune response response to other organism defense response defense response to symbiont response to external stimulus response to peptide response to chemical defense response to other organism type I interferon-mediated signaling pathway response to type I interferon regulation of protein sumoylation regulation of protein modification process positive regulation of protein metabolic process positive regulation of post-translational protein modification positive regulation of protein modification process regulation of protein modification by small protein conjugation or removal positive regulation of protein modification by small protein conjugation or removal regulation of post-translational protein modification regulation of protein metabolic process positive regulation of protein sumoylation cellular developmental process hemopoiesis cell development mononuclear cell differentiation lymphocyte differentiation B cell differentiation cell differentiation leukocyte differentiation negative regulation of DNA-binding transcription factor activity negative regulation of molecular function response to interleukin-1 cellular component organization chromatin organization chromatin remodeling cellular component organization or biogenesis epigenetic regulation of gene expression negative regulation of gene expression negative regulation of gene expression, epigenetic regulation of developmental process negative regulation of muscle cell differentiation regulation of cell differentiation regulation of striated muscle cell differentiation muscle cell differentiation myotube differentiation muscle structure development negative regulation of myotube differentiation regulation of myotube differentiation negative regulation of cell differentiation negative regulation of developmental process negative regulation of striated muscle cell differentiation regulation of muscle cell differentiation striated muscle cell differentiation cell population proliferation positive regulation of cell population proliferation regulation of cell population proliferation negative regulation of transcription by competitive promoter binding inflammatory response regulation of protein binding regulation of binding muscle hypertrophy striated muscle adaptation striated muscle hypertrophy cardiac muscle adaptation cardiac muscle hypertrophy cardiac muscle hypertrophy in response to stress muscle hypertrophy in response to stress	membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen nuclear speck nuclear body intracellular organelle cellular anatomical structure nucleoplasm organelle lumen organelle nuclear lumen membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen nuclear speck nuclear body intracellular organelle cellular anatomical structure nucleoplasm organelle lumen organelle nuclear lumen cytoplasm cytosol membraneless organelle intracellular membraneless organelle chromatin chromosome protein-containing complex catalytic complex nuclear protein-containing complex histone deacetylase complex transcription regulator complex transcription repressor complex

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D	IPR000286	Histone deacetylase family	Family
A, B, C, D	IPR023801	Histone deacetylase domain	Domain
A, B, C, D	IPR046949	Histone deacetylase 4/5/7/9	Family
A, B, C, D	IPR024643	Histone deacetylase, glutamine rich N-terminal domain	Domain
A, B, C, D	IPR037138	Histone deacetylase domain superfamily	Homologous Superfamily
A, B, C, D	IPR023696	Ureohydrolase domain superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D	Pharos: P56524	2q37 microdeletion syndrome brachydactyly intellectual disability malignant mesothelioma urinary bladder cancer cocaine abuse contact dermatitis Familial Primary Pulmonary Hypertension cocaine dependence lung cancer medulloblastoma osteosarcoma primary cutaneous T-cell lymphoma chronic obstructive pulmonary disease schizophrenia 2q37 microdeletion syndrome brachydactyly intellectual disability malignant mesothelioma urinary bladder cancer cocaine abuse contact dermatitis Familial Primary Pulmonary Hypertension cocaine dependence lung cancer medulloblastoma osteosarcoma primary cutaneous T-cell lymphoma chronic obstructive pulmonary disease schizophrenia facioscapulohumeral muscular dystrophy glioblastoma invasive ductal breast carcinoma malignant ependymoma amyotrophic lateral sclerosis ovarian cancer brachydactyly type E1 subependymal giant cell astrocytoma urinary bladder neoplasm idiopathic pulmonary arterial hypertension large cell medulloblastoma malignant glioma mature T-cell and NK-cell non-Hodgkin lymphoma myopathy atypical teratoid rhabdoid tumor plasma cell myeloma psoriasis tuberculosis gastric carcinoma

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.