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5a2s

Potent, selective and CNS-penetrant tetrasubstituted cyclopropane class IIa histone deacetylase (HDAC) inhibitors

Method: X-RAY DIFFRACTION Dmax: 106.4 Å Quality: GOOD
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1. Protein Identity and Related Structures Protein Identity & Related Structures

HISTONE DEACETYLASE 4

HOMO SAPIENS

UniProt P56524

State in the Current Structure

Assembly Oligomeric State Construct Mutations and Modifications Ligands, Ions and Associated Components Method and Experimental Conditions Structure Quality
1 Protein monomer Monomer Protein × 1 PDB declaration: monomeric（1） Consistent with protein copy count Chain A； UniProt 648–1033 Fragment：HISTONE DEACETYLASE DOMAIN, RESIDUES 648-1033 Mutation：YES OTF (1S,2S,3S)-1-fluoranyl-2-[4-(5-fluoranylpyrimidin-2-yl)phenyl]-N-oxidanyl-3-phenyl-cyclopropane-1-carboxamide × 1 ZN ZINC ION × 2 NA SODIUM ION × 1 X-RAY DIFFRACTION X-ray crystallization conditions：24% W/V PEG 3350, 0.2 M AMMONIUM ACETATE, 0.1 M BIS-TRIS PH 5.5, 10 MM PROLINE Resolution 2.65 Å R-free 0.256
2 Protein monomer Monomer Protein × 1 PDB declaration: monomeric（1） Consistent with protein copy count Chain B； UniProt 648–1033 Fragment：HISTONE DEACETYLASE DOMAIN, RESIDUES 648-1033 Mutation：YES OTF (1S,2S,3S)-1-fluoranyl-2-[4-(5-fluoranylpyrimidin-2-yl)phenyl]-N-oxidanyl-3-phenyl-cyclopropane-1-carboxamide × 1 ZN ZINC ION × 2 NA SODIUM ION × 1 X-RAY DIFFRACTION X-ray crystallization conditions：24% W/V PEG 3350, 0.2 M AMMONIUM ACETATE, 0.1 M BIS-TRIS PH 5.5, 10 MM PROLINE Resolution 2.65 Å R-free 0.256

Other States of the Same Protein in the Database

Each row is a biological assembly of the same UniProt protein in another PDB entry. The “Difference from current entry” column identifies evidence-level differences; no tag means the currently parsed fields agree.

Other PDB Difference from Current Entry 5A2S Assembly / Oligomeric State Construct Mutations and Modifications Ligands, Ions and Non-polymers Method and Experimental Conditions Structure Quality
2H8N Structure of a glutamine-rich domain from histone deacetylase 4 Deposited 2006-06-07 Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein homooligomer Homooligomer；Protein × 4 PDB declaration: tetrameric
Chain A 62–153（92 aa） Fragment：N-terminal glutamine-rich Domain, residues 62-129
Chain B 62–153（92 aa） Fragment：N-terminal glutamine-rich Domain, residues 62-129
Chain C 62–153（92 aa） Fragment：N-terminal glutamine-rich Domain, residues 62-129
Chain D 62–153（92 aa） Fragment：N-terminal glutamine-rich Domain, residues 62-129
Not recorded No recorded non-water small molecule X-RAY DIFFRACTION
X-ray crystallization conditions pH 7.5；291 K；0.825M LITHIUM SULFATE, 55mM HEPES PH 7.5, VAPOR DIFFUSION, HANGING DROP, temperature 291K, pH 7.50
Resolution 2.60 Å R-free 0.307
2O94 The 97H/F mutant Structure of a glutamine-rich domain from histone deacetylase 4 Deposited 2006-12-13 Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein homooligomer Homooligomer；Protein × 4 PDB declaration: tetrameric
Chain A 62–153（92 aa） Fragment：N-terminal glutamine-rich domain, residues 62-129
Chain B 62–153（92 aa） Fragment：N-terminal glutamine-rich domain, residues 62-129
Chain C 62–153（92 aa） Fragment：N-terminal glutamine-rich domain, residues 62-129
Chain D 62–153（92 aa） Fragment：N-terminal glutamine-rich domain, residues 62-129
Mutation：H97F Mutation：H97F Mutation：H97F Mutation：H97F No recorded non-water small molecule X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 7.5；298 K；0.540M LITHIUM SULFATE 55mM HEPES PH7.5, VAPOR DIFFUSION, HANGING DROP, temperature 298K
Resolution 3.00 Å R-free 0.327
2VQJ Structure of HDAC4 catalytic domain bound to a trifluoromethylketone inhbitor Deposited 2008-03-17 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 648–1057（410 aa） Fragment：CATALYTIC DOMAIN, RESIDUES 648-1057
Not recorded DIO 1,4-DIETHYLENE DIOXIDE × 1 K POTASSIUM ION × 2 SO4 SULFATE ION × 3 TFG 2,2,2-TRIFLUORO-1-{5-[(3-PHENYL-5,6-DIHYDROIMIDAZO[1,2-A]PYRAZIN-7(8H)-YL)CARBONYL]THIOPHEN-2-YL}ETHANE-1,1-DIOL × 1 ZN ZINC ION × 2 X-RAY DIFFRACTION
X-ray crystallization conditions pH 6.5；1.6M AMMONIUM SULPHATE, 0.1M MES PH 6.5, 10% DIOXANE 1MM DTT
Resolution 2.10 Å R-free 0.276
2VQM Structure of HDAC4 catalytic domain bound to a hydroxamic acid inhbitor Deposited 2008-03-17 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 648–1057（410 aa） Fragment：CATALYTIC DOMAIN, RESIDUES 648-1057
Not recorded K POTASSIUM ION × 2 HA3 N-hydroxy-5-[(3-phenyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)carbonyl]thiophene-2-carboxamide × 1 ZN ZINC ION × 2 X-RAY DIFFRACTION
X-ray crystallization conditions pH 6.4；1.5M AMMONIUM SULPHATE 0.1M MES PH 6.4 10% DIOXANE 1MM DTT
Resolution 1.80 Å R-free 0.256
2VQO Structure of HDAC4 catalytic domain with a gain-of-function muation bound to a trifluoromethylketone inhbitor Deposited 2008-03-18 Different construct Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 648–1057（410 aa） Fragment：CATALYTIC DOMAIN, RESIDUES 648-1057
Mutation：YES SO4 SULFATE ION × 2 K POTASSIUM ION × 2 TFG 2,2,2-TRIFLUORO-1-{5-[(3-PHENYL-5,6-DIHYDROIMIDAZO[1,2-A]PYRAZIN-7(8H)-YL)CARBONYL]THIOPHEN-2-YL}ETHANE-1,1-DIOL × 1 ZN ZINC ION × 1 X-RAY DIFFRACTION
X-ray crystallization conditions pH 6.5；1.6M AMMONIUM SULPHATE, 0.1M MES PH 6.5, 10% DIOXANE, 1MM DTT
Resolution 2.15 Å R-free 0.250
2VQO Structure of HDAC4 catalytic domain with a gain-of-function muation bound to a trifluoromethylketone inhbitor Deposited 2008-03-18 Different construct Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 2 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain B 648–1057（410 aa） Fragment：CATALYTIC DOMAIN, RESIDUES 648-1057
Mutation：YES SO4 SULFATE ION × 1 K POTASSIUM ION × 2 TFG 2,2,2-TRIFLUORO-1-{5-[(3-PHENYL-5,6-DIHYDROIMIDAZO[1,2-A]PYRAZIN-7(8H)-YL)CARBONYL]THIOPHEN-2-YL}ETHANE-1,1-DIOL × 1 ZN ZINC ION × 1 X-RAY DIFFRACTION
X-ray crystallization conditions pH 6.5；1.6M AMMONIUM SULPHATE, 0.1M MES PH 6.5, 10% DIOXANE, 1MM DTT
Resolution 2.15 Å R-free 0.250
2VQQ Structure of HDAC4 catalytic domain (a double cysteine-to-alanine mutant) bound to a trifluoromethylketone inhbitor Deposited 2008-03-18 Different construct Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 648–1057（410 aa） Fragment：CATALYTIC DOMAIN, RESIDUES 648-1057
Mutation：YES SO4 SULFATE ION × 2 K POTASSIUM ION × 2 TFG 2,2,2-TRIFLUORO-1-{5-[(3-PHENYL-5,6-DIHYDROIMIDAZO[1,2-A]PYRAZIN-7(8H)-YL)CARBONYL]THIOPHEN-2-YL}ETHANE-1,1-DIOL × 1 ZN ZINC ION × 1 X-RAY DIFFRACTION
X-ray crystallization conditions pH 6.5；1.6M AMMONIUM SULPHATE, 0.1M MES PH 6.5, 10% DIOXANE 1MM DTT
Resolution 1.90 Å R-free 0.221
2VQQ Structure of HDAC4 catalytic domain (a double cysteine-to-alanine mutant) bound to a trifluoromethylketone inhbitor Deposited 2008-03-18 Different construct Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 2 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain B 648–1057（410 aa） Fragment：CATALYTIC DOMAIN, RESIDUES 648-1057
Mutation：YES SO4 SULFATE ION × 1 K POTASSIUM ION × 2 TFG 2,2,2-TRIFLUORO-1-{5-[(3-PHENYL-5,6-DIHYDROIMIDAZO[1,2-A]PYRAZIN-7(8H)-YL)CARBONYL]THIOPHEN-2-YL}ETHANE-1,1-DIOL × 1 ZN ZINC ION × 1 X-RAY DIFFRACTION
X-ray crystallization conditions pH 6.5；1.6M AMMONIUM SULPHATE, 0.1M MES PH 6.5, 10% DIOXANE 1MM DTT
Resolution 1.90 Å R-free 0.221
2VQV Structure of HDAC4 catalytic domain with a gain-of-function mutation bound to a hydroxamic acid inhibitor Deposited 2008-03-19 Different construct Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 648–1057（410 aa） Fragment：CATALYTIC DOMAIN, RESIDUES 648-1057
Mutation：YES SO4 SULFATE ION × 1 K POTASSIUM ION × 2 HA3 N-hydroxy-5-[(3-phenyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)carbonyl]thiophene-2-carboxamide × 1 ZN ZINC ION × 1 X-RAY DIFFRACTION
X-ray crystallization conditions pH 6.5；0.1M MES PH 6.5, 1.6M AMMONIUM SULPHATE, 10% DIOXANE 1MM DTT
Resolution 3.30 Å R-free 0.265
2VQV Structure of HDAC4 catalytic domain with a gain-of-function mutation bound to a hydroxamic acid inhibitor Deposited 2008-03-19 Different construct Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 2 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain B 648–1057（410 aa） Fragment：CATALYTIC DOMAIN, RESIDUES 648-1057
Mutation：YES SO4 SULFATE ION × 3 K POTASSIUM ION × 2 HA3 N-hydroxy-5-[(3-phenyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)carbonyl]thiophene-2-carboxamide × 1 ZN ZINC ION × 1 X-RAY DIFFRACTION
X-ray crystallization conditions pH 6.5；0.1M MES PH 6.5, 1.6M AMMONIUM SULPHATE, 10% DIOXANE 1MM DTT
Resolution 3.30 Å R-free 0.265
2VQW Structure of inhibitor-free HDAC4 catalytic domain (with gain-of- function mutation His332Tyr) Deposited 2008-03-19 Different construct Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain G 648–1057（410 aa） Fragment：CATALYTIC DOMAIN, RESIDUES 648-1057
Mutation：YES K POTASSIUM ION × 2 ZN ZINC ION × 2 X-RAY DIFFRACTION
X-ray crystallization conditions pH 7.5；0.1M HEPES PH 7.5, 18% PEG 10000, 1MM DTT
Resolution 3.00 Å R-free 0.261
3UXG Crystal structure of RFXANK Deposited 2011-12-05 Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein heterocomplex Heteromer；Protein × 2 PDB declaration: dimeric
Chain B 343–359（17 aa）
Not recorded UNX UNKNOWN LIGAND × 5 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 7.5；291 K；25% PEG3350, 0.2M sodium chloride, 0.1M HEPES, pH 7.5, vapor diffusion, sitting drop, temperature 291K
Resolution 1.85 Å R-free 0.222
3UXG Crystal structure of RFXANK Deposited 2011-12-05 Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 2 Protein heterocomplex Heteromer；Protein × 4 PDB declaration: tetrameric
Chain B 343–359（17 aa）
Not recorded UNX UNKNOWN LIGAND × 10 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 7.5；291 K；25% PEG3350, 0.2M sodium chloride, 0.1M HEPES, pH 7.5, vapor diffusion, sitting drop, temperature 291K
Resolution 1.85 Å R-free 0.222
3UZD Crystal structure of 14-3-3 GAMMA Deposited 2011-12-07 Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein heterocomplex Heteromer；Protein × 8 PDB declaration: octameric
Chain B 343–359（17 aa）
Non-standard monomer：Yes (specific site not provided by mmCIF) NO3 NITRATE ION × 12 MG MAGNESIUM ION × 4 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；291 K；0.3M Mg (OAc)2, 20% PEG3350, vapor diffusion, hanging drop, temperature 291K
Resolution 1.86 Å R-free 0.230
3UZD Crystal structure of 14-3-3 GAMMA Deposited 2011-12-07 Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 2 Protein heterocomplex Heteromer；Protein × 4 PDB declaration: tetrameric
Chain B 343–359（17 aa）
Non-standard monomer：Yes (specific site not provided by mmCIF) NO3 NITRATE ION × 6 MG MAGNESIUM ION × 2 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；291 K；0.3M Mg (OAc)2, 20% PEG3350, vapor diffusion, hanging drop, temperature 291K
Resolution 1.86 Å R-free 0.230
3UZD Crystal structure of 14-3-3 GAMMA Deposited 2011-12-07 Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 3 Protein heterocomplex Heteromer；Protein × 2 PDB declaration: dimeric
Chain B 343–359（17 aa）
Non-standard monomer：Yes (specific site not provided by mmCIF) NO3 NITRATE ION × 3 MG MAGNESIUM ION × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；291 K；0.3M Mg (OAc)2, 20% PEG3350, vapor diffusion, hanging drop, temperature 291K
Resolution 1.86 Å R-free 0.230
3V31 Crystal Structure of the Peptide Bound Complex of the Ankyrin Repeat Domains of Human ANKRA2 Deposited 2011-12-12 Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein heterocomplex Heteromer；Protein × 2 PDB declaration: dimeric
Chain B 343–359（17 aa）
Non-standard monomer：Yes (specific site not provided by mmCIF) CL CHLORIDE ION × 1 NA SODIUM ION × 2 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 6.5；291 K；0.1M Bis-Tris, pH 6.5, 0.2M NaCl, 25% PEG3350, VAPOR DIFFUSION, HANGING DROP, temperature 291K
Resolution 1.57 Å R-free 0.204
4CBT Design, synthesis, and biological evaluation of potent and selective Class IIa HDAC inhibitors as a potential therapy for Huntington's disease Deposited 2013-10-16 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 648–1033（386 aa） Fragment：CATALYTIC DOMAIN, RESIDUES 648-1033
Not recorded 9F4 (1R,2R,3R)-2-[4-(5-fluoranylpyrimidin-2-yl)phenyl]-N-oxidanyl-3-phenyl-cyclopropane-1-carboxamide × 1 ZN ZINC ION × 2 X-RAY DIFFRACTION
X-ray crystallization conditions pH 6.5；0.1 M BISTRIS PH 6.5, 22% PEG MME 5000
Resolution 3.03 Å R-free 0.273
4CBT Design, synthesis, and biological evaluation of potent and selective Class IIa HDAC inhibitors as a potential therapy for Huntington's disease Deposited 2013-10-16 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 2 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain B 648–1033（386 aa） Fragment：CATALYTIC DOMAIN, RESIDUES 648-1033
Not recorded 9F4 (1R,2R,3R)-2-[4-(5-fluoranylpyrimidin-2-yl)phenyl]-N-oxidanyl-3-phenyl-cyclopropane-1-carboxamide × 1 ZN ZINC ION × 2 X-RAY DIFFRACTION
X-ray crystallization conditions pH 6.5；0.1 M BISTRIS PH 6.5, 22% PEG MME 5000
Resolution 3.03 Å R-free 0.273
4CBT Design, synthesis, and biological evaluation of potent and selective Class IIa HDAC inhibitors as a potential therapy for Huntington's disease Deposited 2013-10-16 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 3 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain C 648–1033（386 aa） Fragment：CATALYTIC DOMAIN, RESIDUES 648-1033
Not recorded 9F4 (1R,2R,3R)-2-[4-(5-fluoranylpyrimidin-2-yl)phenyl]-N-oxidanyl-3-phenyl-cyclopropane-1-carboxamide × 1 ZN ZINC ION × 2 X-RAY DIFFRACTION
X-ray crystallization conditions pH 6.5；0.1 M BISTRIS PH 6.5, 22% PEG MME 5000
Resolution 3.03 Å R-free 0.273
4CBY Design, synthesis, and biological evaluation of potent and selective Class IIa HDAC inhibitors as a potential therapy for Huntington's disease Deposited 2013-10-17 Different construct Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 648–1033（386 aa） Fragment：CATALYTIC DOMAIN, RESIDUES 648-1033
Mutation：YES KEE (1R,2R,3R)-2-[4-(1,3-oxazol-5-yl)phenyl]-N-oxidanyl-3-phenyl-cyclopropane-1-carboxamide × 1 ZN ZINC ION × 2 NA SODIUM ION × 2 X-RAY DIFFRACTION
X-ray crystallization conditions pH 6.5；18-24% (W/V) PEG 3350, 0.2 M NACL AND 100 MM BIS-TRIS PH 5.5
Resolution 2.72 Å R-free 0.246
4CBY Design, synthesis, and biological evaluation of potent and selective Class IIa HDAC inhibitors as a potential therapy for Huntington's disease Deposited 2013-10-17 Different construct Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 2 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain B 648–1033（386 aa） Fragment：CATALYTIC DOMAIN, RESIDUES 648-1033
Mutation：YES KEE (1R,2R,3R)-2-[4-(1,3-oxazol-5-yl)phenyl]-N-oxidanyl-3-phenyl-cyclopropane-1-carboxamide × 1 ZN ZINC ION × 2 NA SODIUM ION × 2 X-RAY DIFFRACTION
X-ray crystallization conditions pH 6.5；18-24% (W/V) PEG 3350, 0.2 M NACL AND 100 MM BIS-TRIS PH 5.5
Resolution 2.72 Å R-free 0.246
4CBY Design, synthesis, and biological evaluation of potent and selective Class IIa HDAC inhibitors as a potential therapy for Huntington's disease Deposited 2013-10-17 Different construct Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 3 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain C 648–1033（386 aa） Fragment：CATALYTIC DOMAIN, RESIDUES 648-1033
Mutation：YES KEE (1R,2R,3R)-2-[4-(1,3-oxazol-5-yl)phenyl]-N-oxidanyl-3-phenyl-cyclopropane-1-carboxamide × 1 ZN ZINC ION × 2 NA SODIUM ION × 2 X-RAY DIFFRACTION
X-ray crystallization conditions pH 6.5；18-24% (W/V) PEG 3350, 0.2 M NACL AND 100 MM BIS-TRIS PH 5.5
Resolution 2.72 Å R-free 0.246
4CBY Design, synthesis, and biological evaluation of potent and selective Class IIa HDAC inhibitors as a potential therapy for Huntington's disease Deposited 2013-10-17 Different construct Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 4 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain D 648–1033（386 aa） Fragment：CATALYTIC DOMAIN, RESIDUES 648-1033
Mutation：YES KEE (1R,2R,3R)-2-[4-(1,3-oxazol-5-yl)phenyl]-N-oxidanyl-3-phenyl-cyclopropane-1-carboxamide × 1 ZN ZINC ION × 2 NA SODIUM ION × 2 X-RAY DIFFRACTION
X-ray crystallization conditions pH 6.5；18-24% (W/V) PEG 3350, 0.2 M NACL AND 100 MM BIS-TRIS PH 5.5
Resolution 2.72 Å R-free 0.246
5ZOO Crystal structure of histone deacetylase 4 (HDAC4) in complex with a SMRT corepressor SP1 fragment Deposited 2018-04-13 Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein heterocomplex Heteromer；Protein × 2 PDB declaration: dimeric
Chain G 652–1053（402 aa） Fragment：UNP residues 652-1052
Mutation：H976Y K POTASSIUM ION × 2 ZN ZINC ION × 2 X-RAY DIFFRACTION
X-ray crystallization conditions EVAPORATION；pH 7.5；295 K；PEG 3350, iso-propanol
Resolution 1.85 Å R-free 0.175
5ZOP Crystal structure of histone deacetylase 4 (HDAC4) in complex with a SMRT corepressor SP2 fragment Deposited 2018-04-13 Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein heterocomplex Heteromer；Protein × 2 PDB declaration: dimeric
Chain G 652–1050（399 aa） Fragment：UNP residues 652-1050
Mutation：H976Y K POTASSIUM ION × 2 ZN ZINC ION × 2 X-RAY DIFFRACTION
X-ray crystallization conditions EVAPORATION；pH 7.5；295 K；PEG 3350, iso-propanol
Resolution 2.70 Å R-free 0.235
6FYZ Development and characterization of a CNS-penetrant benzhydryl hydroxamic acid class IIa histone deacetylase inhibitor Deposited 2018-03-13 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 648–1033（386 aa）
Not recorded EBE (2~{S})-2-(2-fluorophenyl)-2-[4-(2-methylpyrimidin-5-yl)phenyl]-~{N}-oxidanyl-ethanamide × 1 ZN ZINC ION × 2 NA SODIUM ION × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 6.5；293 K；0.1 M BisTris, 18 to 24% PEG MME 5000
Resolution 2.15 Å R-free 0.228
6FYZ Development and characterization of a CNS-penetrant benzhydryl hydroxamic acid class IIa histone deacetylase inhibitor Deposited 2018-03-13 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 2 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain B 648–1033（386 aa）
Not recorded EBE (2~{S})-2-(2-fluorophenyl)-2-[4-(2-methylpyrimidin-5-yl)phenyl]-~{N}-oxidanyl-ethanamide × 1 ZN ZINC ION × 2 NA SODIUM ION × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 6.5；293 K；0.1 M BisTris, 18 to 24% PEG MME 5000
Resolution 2.15 Å R-free 0.228
6FYZ Development and characterization of a CNS-penetrant benzhydryl hydroxamic acid class IIa histone deacetylase inhibitor Deposited 2018-03-13 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 3 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain C 648–1033（386 aa）
Not recorded EBE (2~{S})-2-(2-fluorophenyl)-2-[4-(2-methylpyrimidin-5-yl)phenyl]-~{N}-oxidanyl-ethanamide × 1 ZN ZINC ION × 2 NA SODIUM ION × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 6.5；293 K；0.1 M BisTris, 18 to 24% PEG MME 5000
Resolution 2.15 Å R-free 0.228
7XUZ Crystal structure of a HDAC4-MEF2A-DNA ternary complex Deposited 2022-05-20 Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein–DNA Heteromer；Protein × 6 PDB declaration: decameric
Chain A 62–192（131 aa）
Chain B 62–192（131 aa）
Not recorded No recorded non-water small molecule X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；293 K；0 mM HEPES pH 7.5, 0.2 M NaCl, 3% (v/v) PEG 4000
Resolution 3.59 Å R-free 0.298

17 other PDB entries and 30 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence
UniProt name HDAC4_HUMAN
Isoform —
PDB entities 1
Chains and sequence ranges Author chain A； PDBConstruct 4–389； UniProt 648–1033 Author chain B； PDBConstruct 4–389； UniProt 648–1033

The page prioritizes protein identity, the current assembly, associated components, oligomeric state and cross-PDB links. Chain mapping and sequence ranges are retained as data evidence. Internal IDs, import timestamps and assembly operation expressions are maintenance fields and are not shown here.

SAXS scattering curve SAXS Profile

SAXS profile for 5a2s

P(r) Distance Distribution P(r) Distribution

P(r) distribution for 5a2s
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2. Structure Basics 2. Structure Basics

Entry ID entry_id5a2s
Deposition date deposition_date2015-05-22
Structure title titlePotent, selective and CNS-penetrant tetrasubstituted cyclopropane class IIa histone deacetylase (HDAC) inhibitors
Keywords keywords;HYDROLASE, CLASS IIA HDAC INHIBITORS, HYDROXAMIC ACID, CNS EXPOSURE, TETRASUBSTITUTED CYCLOPROPANE, CYCLOPROPANATION, HUNTINGTON'S DISEASE ;; HYDROLASE
Experimental Method methodX-RAY DIFFRACTION
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3. SAXS Parameters (CRYSOL theoretical calculation) 3. SAXS Parameters (CRYSOL)

Radius of gyration Rg (Guinier) rg_guinier30.20 Å
Radius of gyration Rg (electron density) rg_electron29.87 Å
Forward intensity I(0) i0108370000.00
Molecular weight molecular_weight81283.0 kDa
Excluded volume excluded_volume100970 ų
Envelope volume envelope_volume120330 ų
Hydration-shell volume shell_volume34553 ų
Envelope diameter envelope_diameter116.4 Å
Shell Rg shell_rg35.93 Å
Envelope Rg envelope_rg30.07 Å
Shape Rg shape_rg29.85 Å
Total Rg total_rg30.42 Å
Total atoms total_atoms5696
Residues n_residues760
Spherical-harmonic order n_harmonics20
q range q_range— – 0.5000 Å−1
Data points n_points101
Shell type shell_typedirectional
Solvent electron density solvent_density0.3340 e/ų
Shell contrast contrast_shell0.0300 e/ų
CRYSOL version crysol_version4.1.3
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4. P(r) Distance Distribution (GNOM inversion) 4. P(r) Analysis (GNOM)

Maximum dimension Dmax dmax106.4 Å
Rg (real space) rg_real30.37 Å
Rg uncertainty (real space) rg_real_error1.10 Å
I(0) (real space) i0_real1.0840e+08
I(0) uncertainty (real space) i0_real_error1.6700e+06
Rg (reciprocal space) rg_reciprocal30.30 Å
I(0) (reciprocal space) i0_reciprocal108400000.0000
Solution quality estimate total_estimate0.8372
Solution quality rating solution_quality GOOD a GOOD solution
P(r) peaks n_peaks2
Primary peak position r_peak_primary28.6 Å
Skewness Skewness skewness0.514
Kurtosis Kurtosis kurtosis-0.246
Angular range angular_range— – 0.2600 Å−1
Current regularization parameter α current_alpha0.0000
Highest regularization parameter α highest_alpha27840000.0000
Real-space data points n_real_points53
GNOM version gnom_version4.1.3
Quality Criteria quality_criteria AN1: 0.000; Oscil: 0.692; Stabil: 0.996; Sysdev: 1.000; Positv: 1.000; Valcen: 0.840; Smooth: 0.976
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5. Crystallography and Experiment 5. Crystallography & Experiment

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6. Entities and Polymers Entities & Polymers (5)

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7. Fold Classification (SCOP + CATH) 4 domains

SCOP 2.08 (2 domains)

Domain ID domain_idd5a2sa_
Class classc — Alpha and beta proteins (a/b)
Fold Fold foldc.42 — Arginase/deacetylase
Superfamily Superfamily superfamilyc.42.1 — Arginase/deacetylase
Family Family familyc.42.1.2 — Histone deacetylase, HDAC
Domain ID domain_idd5a2sb_
Class classc — Alpha and beta proteins (a/b)
Fold Fold foldc.42 — Arginase/deacetylase
Superfamily Superfamily superfamilyc.42.1 — Arginase/deacetylase
Family Family familyc.42.1.2 — Histone deacetylase, HDAC

CATH v4.4 (2 domains)

Domain ID domain_id5a2sA00
Class class3 — Alpha Beta
Architecture architecture40 — 3-Layer(aba) Sandwich
Topology topology800 — Arginase; Chain A
Homologous superfamily homologous superfamily20 — Histone deacetylase domain
Domain ID domain_id5a2sB00
Class class3 — Alpha Beta
Architecture architecture40 — 3-Layer(aba) Sandwich
Topology topology800 — Arginase; Chain A
Homologous superfamily homologous superfamily20 — Histone deacetylase domain
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8. Citations (1)

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9. Files and Curves (10)