7JS8: Human HDAC2

Structure of human HDAC2 in complex with an ethyl ketone inhibitor containing a spiro-bicyclic group (compound 22). Determined by X-ray diffraction at 1.63 Å resolution. Released 11 Aug 2021.

Method: X-ray diffraction
Resolution: 1.63 Å
Organism: Homo sapiens
Chains: 3
Atoms: 10,368
Mol. weight: 132.93 kDa
Ligands: ZN, CA, VJV
Released: 11 Aug 2021

Explore 7JS8 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7JS8 contains 57 α-helices and 50 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: 19 helices, 16 β-strands

Element	Residues	Length	Sheet
β-strand	12-15	4	1
α-helix	20-22	3
α-helix	34-45	12
α-helix	48-51	4
β-strand	53-55	3	1
α-helix	56-58	3
α-helix	62-65	4
α-helix	71-79	9
α-helix	85-88	4
α-helix	89-94	6
α-helix	107-126	20
β-strand	132-135	4	1
β-strand	144	1	2
β-strand	147	1	2
β-strand	149	1	3
β-strand	152	1	3
α-helix	156-164	9
β-strand	171-175	5	1
α-helix	182-187	6
β-strand	194-201	8	1
α-helix	218-220	3
β-strand	224-229	6	1
α-helix	235-253	19
β-strand	257-261	5	1
α-helix	264-266	3
β-strand	267	1	4
β-strand	277	1	4
α-helix	279-290	12
β-strand	296-299	4	1
α-helix	306-320	15
β-strand	328	1	5
α-helix	329-331	3
α-helix	335-338	4
β-strand	343	1	5
α-helix	357-371	15

Chain B: 19 helices, 18 β-strands

Element	Residues	Length	Sheet
β-strand	12-15	4	6
α-helix	20-22	3
α-helix	34-45	12
α-helix	48-51	4
β-strand	53-55	3	6
α-helix	56-58	3
α-helix	62-65	4
α-helix	71-79	9
α-helix	85-87	3
α-helix	89-94	6
α-helix	107-126	20
β-strand	132-135	4	6
β-strand	144	1	7
β-strand	147	1	7
β-strand	149	1	8
β-strand	152	1	8
α-helix	156-165	10
β-strand	171-175	5	6
α-helix	182-187	6
β-strand	194-201	8	6
α-helix	218-220	3
β-strand	224-229	6	6
β-strand	234	1	9
α-helix	235-253	19
β-strand	257-261	5	6
α-helix	264-266	3
β-strand	267	1	10
β-strand	276	1	9
β-strand	277	1	10
α-helix	279-290	12
β-strand	296-299	4	6
α-helix	306-321	16
β-strand	328	1	11
α-helix	329-331	3
α-helix	335-338	4
β-strand	343	1	11
α-helix	357-371	15

Chain C: 19 helices, 16 β-strands

Element	Residues	Length	Sheet
β-strand	12-15	4	12
α-helix	20-22	3
α-helix	34-45	12
α-helix	49-51	3
β-strand	53-55	3	12
α-helix	56-61	6
α-helix	62-65	4
α-helix	71-79	9
α-helix	85-88	4
α-helix	89-94	6
α-helix	107-126	20
β-strand	132-135	4	12
β-strand	144	1	13
β-strand	147	1	13
β-strand	149	1	14
β-strand	152	1	14
α-helix	156-164	9
β-strand	171-175	5	12
α-helix	182-187	6
β-strand	194-201	8	12
α-helix	218-220	3
β-strand	224-229	6	12
α-helix	235-253	19
β-strand	257-261	5	12
α-helix	264-266	3
β-strand	267	1	15
β-strand	277	1	15
α-helix	279-290	12
β-strand	296-299	4	12
α-helix	306-320	15
β-strand	328	1	16
α-helix	329-331	3
α-helix	335-338	4
β-strand	343	1	16
α-helix	357-372	16

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Histone deacetylase 2	A, B, C	protein	376	Homo sapiens	Q92769 (AlphaFold model)

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

>7JS8_1 Histone deacetylase 2 (chains A, B, C)
MAYSQGGGKKKVCYYYDGDIGNYYYGQGHPMKPHRIRMTHNLLLNYGLYRKMEIYRPHKA
TAEEMTKYHSDEYIKFLRSIRPDNMSEYSKQMQRFNVGEDCPVFDGLFEFCQLSTGGSVA
GAVKLNRQQTDMAVNWAGGLHHAKKSEASGFCYVNDIVLAILELLKYHQRVLYIDIDIHH
GDGVEEAFYTTDRVMTVSFHKYGEYFPGTGDLRDIGAGKGKYYAVNFPMRDGIDDESYGQ
IFKPIISKVMEMYQPSAVVLQCGADSLSGDRLGCFNLTVKGHAKCVEVVKTFNLPLLMLG
GGGYTIRNVARCWTYETAVALDCEIPNELPYNDYFEYFGPDFKLHISPSNMTNQNTPEYM
EKIKQRLFENLRMLPH

Ligands and cofactors

ID	Name	Formula	Copies
ZN	Zinc ion	Zn	3
CA	Calcium ion	Ca	6
VJV	(1S)-N-{(1S)-7,7-dihydroxy-1-[4-(2-methylquinolin-6-yl)-1H-imidazol-2-yl]nonyl}…	C31 H43 N5 O3	3

Water and common crystallization additives (SO4, PEG) are not listed.

Primary citation

Discovery of Ethyl Ketone-Based Highly Selective HDACs 1, 2, 3 Inhibitors for HIV Latency Reactivation with Minimum Cellular Potency Serum Shift and Reduced hERG Activity. Yu, W., Liu, J., Clausen, D. et al. J Med Chem (2021) 64:4709-4729. DOI 10.1021/acs.jmedchem.0c02150 · PubMed

Other PDB entries of the same protein (UniProt Q92769 (AlphaFold model), which also has an AlphaFold model), best resolution first:

7KBG 1.26 Å, Structure of Human HDAC2 in complex with a 2-substituted benzamide inhibitor (compound 20)
6WBZ 1.32 Å, Structure of Human HDAC2 in complex with an ethyl ketone inhibitor containing a…
6WBW 1.46 Å, Structure of Human HDAC2 in complex with an ethyl ketone inhibitor
7LTL 1.49 Å, Structure of human HDAC2 in complex with an inhibitor lacking a zinc binding group…
6XEB 1.5 Å, Structure of human HDAC2 in complex with ketone inhibitor (compound E)
7ZZP 1.52 Å, Structure of HDAC2 complexed with an inhibitory ligand
6WHN 1.54 Å, Histone deacetylases complex with peptide macrocycles
7MOT 1.54 Å, Structure of HDAC2 in complex with an inhibitor (compound 9)
7MOZ 1.54 Å, Structure of HDAC2 in complex with a macrocyclic inhibitor (compound 25)
6XDM 1.56 Å, Structure of human HDAC2 in complex with an aryl ketone inhibitor
7ZZT 1.56 Å, Ligand binding to HDAC2
4LY1 1.57 Å, Structure of Human HDAC2 in complex with inhibitor 4-(acetylamino)-N-[2-amino-5-(thiophen…

Browse structure collections

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