6TUY: Human LSD1/CoREST

Human LSD1/CoREST bound to the quinazoline inhibitor MC4106. Determined by X-ray diffraction at 2.6 Å resolution. Released 21 Jul 2021.

Method: X-ray diffraction
Resolution: 2.6 Å
Organism: Homo sapiens
Chains: 2
Atoms: 6,536
Mol. weight: 149.32 kDa
Ligands: PO4, NY8, FAD
Released: 21 Jul 2021

Explore 6TUY in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

6TUY contains 38 α-helices and 34 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, 34 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	231-237	7
α-helix	246-258	13
β-strand	268	1	1
α-helix	272-273	2
β-strand	280-284	5	2
α-helix	288-299	12
β-strand	303-307	5	2
β-strand	319-322	4	3
β-strand	325-328	4	3
β-strand	333-334	2	4
β-strand	338	1	5
α-helix	341-348	8
β-strand	353-355	3	4
β-strand	363	1	6
β-strand	369	1	6
α-helix	372-394	23
β-strand	400-401	2	7
β-strand	404-405	2	7
α-helix	406	1
β-strand	407	1	8
α-helix	408-467	60
α-helix	469	1
α-helix	474-513	40
α-helix	515-517	3
α-helix	523-539	17
β-strand	547	1	9
β-strand	548	1	8
α-helix	556-558	3
β-strand	561	1	5
β-strand	565-567	3	4
α-helix	573-578	6
β-strand	584-585	2	2
β-strand	588-596	9	10
β-strand	599-606	8	10
β-strand	613-618	6	10
β-strand	620-623	4	2
α-helix	627-631	5
β-strand	638-640	3	10
α-helix	642-644	3
α-helix	645-653	9
β-strand	655-656	2	11
β-strand	660-665	6	12
β-strand	677-679	3	12
β-strand	693-696	4	12
β-strand	702-707	6	12
α-helix	709-716	8
α-helix	720-735	16
α-helix	737-739	3
α-helix	741-743	3
β-strand	745-748	4	12
β-strand	762-763	2	11
β-strand	765	1	9
α-helix	771-777	7
β-strand	780	1	2
α-helix	782-784	3
β-strand	796-798	3	2
α-helix	801-803	3
α-helix	811-830	20
α-helix	833-835	3

Chain B: 8 helices, 0 β-strands

Element	Residues	Length
α-helix	310	1
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	430-440	11

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Lysine-specific histone demethylase 1A	A	protein	853	Homo sapiens	O60341 (AlphaFold model)
REST corepressor 1	B	protein	485	Homo sapiens	Q9UKL0 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>6TUY_1 Lysine-specific histone demethylase 1A (chains A)
MLSGKKAAAAAAAAAAAATGTEAGPGTAGGSENGSEVAAQPAGLSGPAEVGPGAVGERTP
RKKEPPRASPPGGLAEPPGSAGPQAGPTVVPGSATPMETGIAETPEGRRTSRRKRAKVEY
REMDESLANLSEDEYYSEEERNAKAEKEKKLPPPPPQAPPEEENESEPEEPSGVEGAAFQ
SRLPHDRMTSQEAACFPDIISGPQQTQKVFLFIRNRTLQLWLDNPKIQLTFEATLQQLEA
PYNSDTVLVHRVHSYLERHGLINFGIYKRIKPLPTKKTGKVIIIGSGVSGLAAARQLQSF
GMDVTLLEARDRVGGRVATFRKGNYVADLGAMVVTGLGGNPMAVVSKQVNMELAKIKQKC
PLYEANGQAVPKEKDEMVEQEFNRLLEATSYLSHQLDFNVLNNKPVSLGQALEVVIQLQE
KHVKDEQIEHWKKIVKTQEELKELLNKMVNLKEKIKELHQQYKEASEVKPPRDITAEFLV
KSKHRDLTALCKEYDELAETQGKLEEKLQELEANPPSDVYLSSRDRQILDWHFANLEFAN
ATPLSTLSLKHWDQDDDFEFTGSHLTVRNGYSCVPVALAEGLDIKLNTAVRQVRYTASGC
EVIAVNTRSTSQTFIYKCDAVLCTLPLGVLKQQPPAVQFVPPLPEWKTSAVQRMGFGNLN
KVVLCFDRVFWDPSVNLFGHVGSTTASRGELFLFWNLYKAPILLALVAGEAAGIMENISD
DVIVGRCLAILKGIFGSSAVPQPKETVVSRWRADPWARGSYSYVAAGSSGNDYDLMAQPI
TPGPSIPGAPQPIPRLFFAGEHTIRNYPATVHGALLSGLREAGRIADQFLGAMYTLPRQA
TPGVPAQQSPSMP

Sequence of entity 2 (B), FASTA

>6TUY_2 REST corepressor 1 (chains B)
MPAMVEKGPEVSGKRRGRNNAAASASAAAASAAASAACASPAATAASGAAASSASAAAAS
AAAAPNNGQNKSLAAAAPNGNSSSNSWEEGSSGSSSDEEHGGGGMRVGPQYQAVVPDFDP
AKLARRSQERDNLGMLVWSPNQNLSEAKLDEYIAIAKEKHGYNMEQALGMLFWHKHNIEK
SLADLPNFTPFPDEWTVEDKVLFEQAFSFHGKTFHRIQQMLPDKSIASLVKFYYSWKKTR
TKTSVMDRHARKQKREREESEDELEEANGNNPIDIEVDQNKESKKEVPPTETVPQVKKEK
HSTQAKNRAKRKPPKGMFLSQEDVEAVSANATAATTVLRQLDMELVSVKRQIQNIKQTNS
ALKEKLDGGIEPYRLPEVIQKCNARWTTEEQLLAVQAIRKYGRDFQAISDVIGNKSVVQV
KNFFVNYRRRFNIDEVLQEWEAEHGKEETNGPSNQKPVKSPDNSIKMPEEEDEAPVLDVR
YASAS

Ligands and cofactors

ID	Name	Formula	Copies
PO4	Phosphate ion	O4 P	1
NY8	~{N}2-[3-(dimethylamino)propyl]-6,7-dimethoxy-~{N}4-[1-(naphthalen-2-ylmethyl)p…	C31 H40 N6 O2	3
FAD	Flavin-adenine dinucleotide	C27 H33 N9 O15 P2	1

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

Primary citation

Novel non-covalent LSD1 inhibitors endowed with anticancer effects in leukemia and solid tumor cellular models. Menna, M., Fiorentino, F., Marrocco, B. et al. Eur J Med Chem (2022) 237:114410-114410. DOI 10.1016/j.ejmech.2022.114410 · 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

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