9GGL: Histone deacetylase 2

Name: PDB 9GGL: Cryo-EM structure of KBTBD4 WT-HDAC2 2:1 complex mediated by molecular glue UM171
Published: 2025-04-09
License: https://creativecommons.org/publicdomain/zero/1.0/
Keywords: ligase

Cryo-EM structure of KBTBD4 WT-HDAC2 2:1 complex mediated by molecular glue UM171. Determined by electron microscopy at 3.13 Å resolution. Released 9 Apr 2025.

Method: Electron microscopy
Resolution: 3.13 Å
Organism: Homo sapiens
Chains: 3
Atoms: 9,006
Mol. weight: 172.38 kDa
Ligands: ZN, A1ACV
Released: 9 Apr 2025

Explore 9GGL in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9GGL contains 48 α-helices and 83 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, 38 β-strands

Element	Residues	Length	Sheet
β-strand	30	1	8
β-strand	34-38	5	8
α-helix	42-50	9
α-helix	51-55	5
β-strand	63-67	5	16
β-strand	71-74	4	16
α-helix	76-82	7
α-helix	86-91	6
β-strand	103-104	2	16
α-helix	109-121	13
β-strand	123-127	5	5
α-helix	131-140	10
α-helix	145-156	12
α-helix	163-173	11
α-helix	176-188	13
α-helix	192-195	4
α-helix	204-210	7
α-helix	217-219	3
α-helix	221-229	9
α-helix	242-245	4
β-strand	256-260	5	17
β-strand	269-276	8	17
β-strand	280-288	9	17
β-strand	293-299	7	18
β-strand	302-307	6	18
β-strand	315-316	2	19
β-strand	317	1	18
β-strand	325-326	2	19
α-helix	328-330	3
β-strand	335	1	20
β-strand	338-342	5	21
β-strand	347-351	5	21
β-strand	354	1	20
β-strand	360	1	20
β-strand	364-368	5	21
β-strand	373-376	4	21
α-helix	378-380	3
β-strand	388-392	5	22
β-strand	395-404	10	22
α-helix	405	1
β-strand	410-420	11	22
β-strand	425-432	8	22
β-strand	439-444	6	23
β-strand	447-452	6	23
β-strand	456-458	3	23
β-strand	461	1	24
β-strand	466	1	24
β-strand	470-471	2	23
α-helix	472-473	2
β-strand	484-486	3	25
β-strand	492-495	4	25
β-strand	498	1	26
β-strand	506-510	5	25
α-helix	512-514	3
β-strand	515-518	4	25
β-strand	528	1	26
β-strand	529-533	5	17

Chain B: 16 helices, 14 β-strands

Element	Residues	Length	Sheet
β-strand	12-15	4	1
α-helix	18-20	3
α-helix	34-45	12
β-strand	53-55	3	1
α-helix	62-65	4
α-helix	71-79	9
β-strand	97	1	2
β-strand	101	1	2
α-helix	107-126	20
β-strand	132-135	4	1
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	194-199	6	1
α-helix	218-220	3
β-strand	225-227	3	1
α-helix	235-252	18
β-strand	257-261	5	1
α-helix	279-282	4
α-helix	285-290	6
β-strand	296-299	4	1
α-helix	306-320	15
β-strand	328	1	4
α-helix	329-330	2
α-helix	335-337	3
β-strand	343	1	4
α-helix	347-350	4
α-helix	357-372	16

Chain C: 13 helices, 31 β-strands

Element	Residues	Length	Sheet
β-strand	34-38	5	5
α-helix	42-51	10
α-helix	52-56	5
β-strand	62	1	6
β-strand	64-67	4	7
β-strand	70-72	3	7
β-strand	75	1	6
α-helix	76-81	6
α-helix	85-91	7
β-strand	101-103	3	7
α-helix	109-120	12
β-strand	123-127	5	8
α-helix	132-140	9
α-helix	144-156	13
α-helix	163-172	10
α-helix	176-187	12
α-helix	204-212	9
α-helix	221-225	5
β-strand	296-298	3	9
β-strand	303-305	3	9
β-strand	315	1	9
α-helix	328-330	3
β-strand	334-335	2	10
β-strand	338-339	2	11
β-strand	347	1	12
β-strand	350-351	2	11
β-strand	354-355	2	10
β-strand	360	1	10
β-strand	365	1	11
β-strand	368	1	12
β-strand	376	1	11
α-helix	378-380	3
β-strand	388-392	5	13
β-strand	395-405	11	13
β-strand	409-420	12	13
β-strand	425-429	5	13
β-strand	440-443	4	14
β-strand	448-451	4	14
β-strand	456-461	6	14
β-strand	466-471	6	14
β-strand	483-487	5	15
β-strand	492-496	5	15
β-strand	507-510	4	15
β-strand	515-518	4	15

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Histone deacetylase 2	B	protein	488	Homo sapiens	Q92769 (AlphaFold model)
Isoform 1 of Kelch repeat and BTB domain-containing protein 4	A, C	protein	518	Homo sapiens	Q9NVX7 (AlphaFold model)

Sequence of entity 1 (B), FASTA

>9GGL_1 Histone deacetylase 2 (chains B)
MAYSQGGGKKKVCYYYDGDIGNYYYGQGHPMKPHRIRMTHNLLLNYGLYRKMEIYRPHKA
TAEEMTKYHSDEYIKFLRSIRPDNMSEYSKQMQRFNVGEDCPVFDGLFEFCQLSTGGSVA
GAVKLNRQQTDMAVNWAGGLHHAKKSEASGFCYVNDIVLAILELLKYHQRVLYIDIDIHH
GDGVEEAFYTTDRVMTVSFHKYGEYFPGTGDLRDIGAGKGKYYAVNFPMRDGIDDESYGQ
IFKPIISKVMEMYQPSAVVLQCGADSLSGDRLGCFNLTVKGHAKCVEVVKTFNLPLLMLG
GGGYTIRNVARCWTYETAVALDCEIPNELPYNDYFEYFGPDFKLHISPSNMTNQNTPEYM
EKIKQRLFENLRMLPHAPGVQMQAIPEDAVHEDSGDEDGEDPDKRISIRASDKRIACDEE
FSDSEDEGEGGRRNVADHKKGAKKARIEEDKKETEDKKTDVKEEDKSKDNSGEKTDTKGT
KSEQLSNP

Sequence of entity 2 (A, C), FASTA

>9GGL_2 Isoform 1 of Kelch repeat and BTB domain-containing protein 4 (chains A, C)
MESPEEPGASMDENYFVNYTFKDRSHSGRVAQGIMKLCLEEELFADVTISVEGREFQLHR
LVLSAQSCFFRSMFTSNLKEAHNRVIVLQDVSESVFQLLVDYIYHGTVKLRAEELQEIYE
VSDMYQLTSLFEECSRFLARTVQVGNCLQVMWLADRHSDPELYTAAKHCAKTHLAQLQNT
EEFLHLPHRLLTDIISDGVPCSQNPTEAIEAWINFNKEEREAFAESLRTSLKEIGENVHI
YLIGKESSRTHSLAVSLHCAEDDSISVSGQNSLCHQITAACKHGGDLYVVGGSIPRRMWK
CNNATVDWEWCAPLPRDRLQHTLVSVPGKDAIYSLGGKTLQDTLSNAVIYYRVGDNVWTE
TTQLEVAVSGAAGANLNGIIYLLGGEENDLDFFTKPSRLIQCFDTETDKCHVKPYVLPFA
GRMHAAVHKDLVFIVAEGDSLVCYNPLLDSFTRLCLPEAWSSAPSLWKIASCNGSIYVFR
DRYKKGDANTYKLDPATSAVTVTRGIKVLLTNLQFVLA

Ligands and cofactors

ID	Name	Formula	Copies
ZN	Zinc ion	Zn	1
A1ACV	(1r,4r)-N~1~-[(7P)-2-benzyl-7-(2-methyl-2H-tetrazol-5-yl)-9H-pyrimido[4,5-b]ind…	C25 H27 N9	1

Primary citation

Structural mimicry of UM171 and neomorphic cancer mutants co-opts E3 ligase KBTBD4 for HDAC1/2 recruitment. Chen, Z., Chi, G., Balo, T. et al. Nat Commun (2025) 16:3144-3144. DOI 10.1038/s41467-025-58350-z · 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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