9DBP: LSD1/CoREST histone demethylase

Crystal structure of the LSD1/CoREST histone demethylase in complex with the cofactor FAD and the inhibitor GSK690. Determined by X-ray diffraction at 2.66 Å resolution. Released 17 Sept 2025.

Method: X-ray diffraction
Resolution: 2.66 Å
Organism: Homo sapiens
Chains: 2
Atoms: 6,282
Mol. weight: 89.45 kDa
Ligands: A1A5U, FAD
Released: 17 Sept 2025

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

Secondary structure: helices and β-sheets

9DBP contains 39 α-helices and 36 β-strands across 2 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: 30 helices, 36 β-strands

Element	Residues	Length	Sheet
α-helix	174-180	7
α-helix	190-195	6
α-helix	197-200	4
α-helix	204-223	20
β-strand	227	1	1
α-helix	231-236	6
α-helix	246-258	13
β-strand	268	1	1
β-strand	280-284	5	2
β-strand	287	1	3
α-helix	288-299	12
β-strand	303-307	5	2
β-strand	314	1	3
β-strand	319-322	4	4
β-strand	325-328	4	4
β-strand	333-334	2	5
β-strand	338	1	6
α-helix	341-349	9
α-helix	351-352	2
β-strand	353-355	3	5
β-strand	362-363	2	7
α-helix	368	1
β-strand	369	1	7
α-helix	370-371	2
α-helix	372-394	23
β-strand	400-401	2	8
β-strand	404-405	2	8
β-strand	407	1	9
α-helix	408-466	59
α-helix	474-513	40
α-helix	523-539	17
α-helix	544-546	3
β-strand	547	1	10
β-strand	548	1	9
α-helix	556-558	3
α-helix	559-560	2
β-strand	561	1	6
β-strand	565-567	3	5
α-helix	573-578	6
β-strand	583-585	3	2
β-strand	588-595	8	11
β-strand	600-606	7	11
β-strand	613-618	6	11
β-strand	620-623	4	2
α-helix	627-630	4
β-strand	638-640	3	11
α-helix	642-644	3
α-helix	645-653	9
β-strand	655-656	2	12
β-strand	660-665	6	7
β-strand	677-680	4	7
β-strand	693-695	3	7
β-strand	702-707	6	7
α-helix	709-715	7
α-helix	720-735	16
α-helix	740-743	4
β-strand	746-748	3	7
β-strand	762-763	2	12
β-strand	765	1	10
α-helix	770-776	7
α-helix	779	1
β-strand	780	1	2
α-helix	789-791	3
β-strand	796-798	3	2
α-helix	801-803	3
α-helix	811-829	19

Chain B: 9 helices, 0 β-strands

Element	Residues	Length
α-helix	310-311	2
α-helix	318-325	8
α-helix	330-362	33
α-helix	368-370	3
α-helix	385-398	14
α-helix	402-409	8
α-helix	414-423	10
α-helix	425-428	4
α-helix	430-437	8

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Lysine-specific histone demethylase 1A	A	protein	660	Homo sapiens	O60341 (AlphaFold model)
REST corepressor 1	B	protein	131	Homo sapiens	Q9UKL0 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>9DBP_1 Lysine-specific histone demethylase 1A (chains A)
SGVEGAAFQSRLPHDRMTSQEAACFPDIISGPQQTQKVFLFIRNRTLQLWLDNPKIQLTF
EATLQQLEAPYNSDTVLVHRVHSYLERHGLINFGIYKAIKPLPTKKTGKVIIIGSGVSGL
AAARQLQSFGMDVTLLEARDRVGGRVATFRKGNYVADLGAMVVTGLGGNPMAVVSKQVNM
ELAKIKQKCPLYEANGQAVPKEKDEMVEQEFNRLLEATSYLSHQLDFNVLNNKPVSLGQA
LEVVIQLQEKHVKDEQIEHWKKIVKTQEELKELLNKMVNLKEKIKELHQQYKEASEVAPP
RDITAEFLVKSKHRDLTALCKEYDELAETQGKLEEKLQELEANPPSDVYLSSRDRQILDW
HFANLEFANATPLSTLSLKHWDQDDDFEFTGSHLTVRNGYSCVPVALAEGLDIKLNTAVR
QVRYTASGCEVIAVNTRSTSQTFIYKCDAVLCTLPLGVLKQQPPAVQFVPPLPEWKTSAV
QRMGFGNLNKVVLCFDRVFWDPSVNLFGHVGSTTASRGELFLFWNLYKAPILLALVAGEA
AGIMENISDDVIVGRCLAILKGIFGSSAVPQPKETVVSRWRADPWARGSYSYVAAGSSGN
DYDLMAQPITPGPSIPGAPQPIPRLFFAGEHTIRNYPATVHGALLSGLREAGRIADQFLG

Sequence of entity 2 (B), FASTA

>9DBP_2 REST corepressor 1 (chains B)
KPPAGMFLSQEDVEAVSANATAATTVLRQLDMELVSVKRQIQNIKQTNSALKEKLDGGIE
PYRLPEVIQACNARWTTEEQLLAVQAIRKYGRDFQAISDVIGNKSVVQVKNFFANYARRF
NIDEVLQEWEA

Ligands and cofactors

ID	Name	Formula	Copies
A1A5U	4-[2-(4-methylphenyl)-5-{[(3R)-pyrrolidin-3-yl]methoxy}pyridin-3-yl]benzonitrile	C24 H23 N3 O	1
FAD	Flavin-adenine dinucleotide	C27 H33 N9 O15 P2	1

Water and common crystallization additives (GOL) are not listed.

Primary citation

Novel, potent, and orally bioavailable LSD1 inhibitors induce fetal hemoglobin synthesis in a sickle cell disease mouse model. Wang, Y., Yu, L., Deng, K. et al. Blood (2025) 146:356-368. DOI 10.1182/blood.2024028006 · PubMed

Other PDB entries of the same protein (UniProt O60341 (AlphaFold model), which also has an AlphaFold model), best resolution first:

6E1F 1.16 Å, Crystal structure of the SWIRM domain of human histone lysine-specific demethylase LSD1
5IT3 1.4 Å, Swirm domain of human Lsd1
5AFW 1.6 Å, Assembly of methylated LSD1 and CHD1 drives AR-dependent transcription and translocation
7JK7 1.96 Å, Crystal structure of Importin alpha 2 in complex with LSD1 NLS S111E mutant
7JJM 2.06 Å, Crystal structure of Importin alpha 2 in complex with LSD1 NLS
2Z3Y 2.25 Å, Crystal structure of Lysine-specific demethylase1
2Z5U 2.25 Å, Crystal structure of Lysine-specific histone demethylase 1
6KGO 2.25 Å, LSD1-S2157 five-membered ring adduct model
6KGP 2.25 Å, LSD1-S2157 N5 adduct model
7E0G 2.25 Å, Crystal structure of Lysine Specific Demethylase 1 (LSD1) with TAK-418, FAD-adduct
7XW8 2.28 Å, Crystal structure of Lysine Specific Demethylase 1 (LSD1) with TAK-418 distomer,…
2DW4 2.3 Å, Crystal structure of human LSD1 at 2.3 A resolution

Browse structure collections

About this viewer

MolViewer shows 9DBP directly in your browser with nothing to install. Switch between cartoon, ball-and-stick, spacefill and surface views, color by chain, secondary structure or B-factor, measure distances, angles and dihedrals, and share or embed the view.