4CBT: Histone deacetylase 4

Design, synthesis, and biological evaluation of potent and selective Class IIa HDAC inhibitors as a potential therapy for Huntington's disease. Determined by X-ray diffraction at 3.03 Å resolution. Released 11 Dec 2013.

Method: X-ray diffraction
Resolution: 3.03 Å
Organism: HOMO SAPIENS
Chains: 3
Atoms: 7,993
Mol. weight: 129.83 kDa
Ligands: ZN, 9F4
Released: 11 Dec 2013

Explore 4CBT in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

4CBT contains 66 α-helices and 40 β-strands across 3 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 22 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	654-657	4	1
α-helix	660-662	3
α-helix	680-691	12
α-helix	694-697	4
β-strand	699-700	2	1
α-helix	701-703	3
α-helix	705-707	3
α-helix	708-711	4
α-helix	717-724	8
α-helix	767-786	20
β-strand	792-795	4	1
α-helix	817-829	13
β-strand	834-838	5	1
α-helix	845-850	6
β-strand	857-864	8	1
α-helix	866-868	3
α-helix	883-885	3
β-strand	889-894	6	1
α-helix	901-902	2
β-strand	903	1	2
α-helix	904-910	7
α-helix	911-915	5
α-helix	916-922	7
β-strand	926-931	6	1
β-strand	936	1	3
β-strand	947	1	2
β-strand	948	1	3
α-helix	950-961	12
α-helix	963-966	4
β-strand	968-972	5	1
α-helix	978-993	16
α-helix	1007-1010	4
α-helix	1011-1024	14
α-helix	1029-1031	3

Chain B: 23 helices, 14 β-strands

Element	Residues	Length	Sheet
β-strand	655-657	3	4
α-helix	660-664	5
α-helix	680-691	12
α-helix	694-697	4
β-strand	699-701	3	4
α-helix	705-707	3
α-helix	708-711	4
α-helix	717-724	8
α-helix	767-787	21
β-strand	793-795	3	4
β-strand	805	1	5
β-strand	808	1	5
β-strand	810	1	6
β-strand	813	1	6
α-helix	817-824	8
α-helix	825-829	5
β-strand	834-838	5	4
α-helix	845-850	6
β-strand	857-864	8	4
α-helix	883-885	3
β-strand	889-894	6	4
α-helix	901-902	2
α-helix	904-910	7
α-helix	911-915	5
α-helix	916-922	7
β-strand	926-931	6	4
β-strand	936	1	7
β-strand	948	1	7
α-helix	952-960	9
α-helix	964-966	3
β-strand	968-972	5	4
α-helix	978-993	16
α-helix	1000-1002	3
α-helix	1003-1007	5
α-helix	1008-1011	4
α-helix	1012-1025	14
α-helix	1030-1032	3

Chain C: 21 helices, 14 β-strands

Element	Residues	Length	Sheet
α-helix	650-651	2
β-strand	654-657	4	8
α-helix	660-664	5
α-helix	680-691	12
α-helix	694-697	4
β-strand	699-700	2	8
α-helix	705-707	3
α-helix	708-711	4
α-helix	717-724	8
α-helix	767-786	20
β-strand	792-795	4	8
β-strand	810	1	9
β-strand	813	1	9
α-helix	817-827	11
β-strand	834-838	5	8
α-helix	845-850	6
β-strand	857-864	8	8
α-helix	883-885	3
β-strand	889-894	6	8
β-strand	903	1	10
α-helix	904-910	7
α-helix	911-915	5
α-helix	916-922	7
β-strand	926-931	6	8
β-strand	936	1	11
β-strand	947	1	10
β-strand	948	1	11
α-helix	952-960	9
α-helix	964-966	3
β-strand	968-972	5	8
α-helix	978-993	16
α-helix	1004-1006	3
α-helix	1008-1010	3
α-helix	1011-1023	13
α-helix	1029-1031	3

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Histone deacetylase 4	A, B, C	protein	395	HOMO SAPIENS	P56524 (AlphaFold model)

Sequence of entity 1 (A, B, C), FASTA

>4CBT_1 HISTONE DEACETYLASE 4 (chains A, B, C)
MGSTKPRFTTGLVYDTLMLKHQCTCGSSSSHPEHAGRIQSIWSRLQETGLRGKCECIRGR
KATLEELQTVHSEAHTLLYGTNPLNRQKLDSKKLLGSLASVFVRLPCGGVGVDSDTIWNE
VHSAGAARLAVGCVVELVFKVATGELKNGFAVVRPPGHHAEESTPMGFCYFNSVAVAAKL
LQQRLSVSKILIVDWDVHHGNGTQQAFYSDPSVLYMSLHRYDDGNFFPGSGAPDEVGTGP
GVGFNVNMAFTGGLDPPMGDAEYLAAFRTVVMPIASEFAPDVVLVSSGFDAVEGHPTPLG
GYNLSARCFGYLTKQLMGLAGGRIVLALEGGHDLTAICDASEACVSALLGNELDPLPEKV
LQQRPNANAVRSMEKVMEIHSKYWRCLQRHHHHHH

Ligands and cofactors

ID	Name	Formula	Copies
ZN	Zinc ion	Zn	6
9F4	(1R,2R,3R)-2-[4-(5-fluoranylpyrimidin-2-yl)phenyl]-N-oxidanyl-3-phenyl-cyclopro…	C20 H16 F N3 O2	3

Primary citation

Design, synthesis, and biological evaluation of potent and selective class IIa histone deacetylase (HDAC) inhibitors as a potential therapy for Huntington's disease. Burli, R.W., Luckhurst, C.A., Aziz, O. et al. J Med Chem (2013) 56:9934-9954. DOI 10.1021/jm4011884 · PubMed

Other PDB entries of the same protein (UniProt P56524 (AlphaFold model), which also has an AlphaFold model), best resolution first:

3V31 1.57 Å, Crystal Structure of the Peptide Bound Complex of the Ankyrin Repeat Domains of Human…
2VQM 1.8 Å, Structure of HDAC4 catalytic domain bound to a hydroxamic acid inhbitor
3UXG 1.85 Å, Crystal structure of RFXANK
5ZOO 1.85 Å, Crystal structure of histone deacetylase 4 (HDAC4) in complex with a SMRT corepressor…
3UZD 1.86 Å, Crystal structure of 14-3-3 GAMMA
2VQQ 1.9 Å, Structure of HDAC4 catalytic domain (a double cysteine-to-alanine mutant) bound to a…
2VQJ 2.1 Å, Structure of HDAC4 catalytic domain bound to a trifluoromethylketone inhbitor
2VQO 2.15 Å, Structure of HDAC4 catalytic domain with a gain-of-function muation bound to a…
6FYZ 2.15 Å, Development and characterization of a CNS-penetrant benzhydryl hydroxamic acid class IIa…
8PDE 2.4 Å, Crystal Structure of the MADS-box/MEF2 Domain of MEF2D bound to dsDNA and HDAC4…
2H8N 2.6 Å, Structure of a glutamine-rich domain from histone deacetylase 4
5A2S 2.65 Å, Potent, selective and CNS-penetrant tetrasubstituted cyclopropane class IIa histone…

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