5LS6: PDB entry 5LS6

Structure of Human Polycomb Repressive Complex 2 (PRC2) with inhibitor. Determined by X-ray diffraction at 3.47 Å resolution. Released 22 Feb 2017.

Method: X-ray diffraction
Resolution: 3.47 Å
Organism: Homo sapiens
Chains: 16
Atoms: 34,891
Mol. weight: 557.89 kDa
Ligands: ZN, 74D
Released: 22 Feb 2017

Explore 5LS6 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

5LS6 contains 153 α-helices and 229 β-strands across 15 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: 28 helices, 26 β-strands

Element	Residues	Length	Sheet
α-helix	12-61	50
α-helix	73	1
α-helix	75-76	2
β-strand	82-87	6	1
α-helix	91-93	3
β-strand	94-97	4	1
β-strand	99-101	3	2
α-helix	105-109	5
β-strand	114-115	2	3
β-strand	120-121	2	4
β-strand	128	1	5
α-helix	135-138	4
α-helix	144-151	8
β-strand	157	1	5
α-helix	168-181	14
α-helix	223-229	7
α-helix	237-247	11
α-helix	274-277	4
α-helix	279-284	6
β-strand	285	1	6
β-strand	292	1	6
α-helix	304-306	3
α-helix	332-343	12
α-helix	426-428	3
α-helix	434-447	14
α-helix	451-458	8
α-helix	463-475	13
α-helix	477-478	2
α-helix	535-538	4
β-strand	543	1	7
β-strand	556	1	7
α-helix	557-558	2
α-helix	572-575	4
β-strand	578	1	8
α-helix	605-608	4
β-strand	614-618	5	9
β-strand	624-628	5	9
β-strand	632	1	10
β-strand	637-639	3	8
β-strand	644-647	4	4
α-helix	648-660	13
β-strand	666-668	3	4
β-strand	673-676	4	4
β-strand	680-681	2	3
α-helix	683-686	4
α-helix	687	1
β-strand	688	1	11
α-helix	689	1
β-strand	695-702	8	8
β-strand	705-712	8	8
β-strand	716	1	10
α-helix	720	1
β-strand	721-722	2	9
β-strand	723	1	11

Chain B: 4 helices, 29 β-strands

Element	Residues	Length	Sheet
β-strand	82-90	9	1
β-strand	96-101	6	2
α-helix	106	1
β-strand	112-117	6	2
β-strand	120-126	7	2
β-strand	132-140	9	2
β-strand	147-154	8	12
β-strand	161-167	7	12
β-strand	172-176	5	12
β-strand	181-186	6	12
β-strand	193-198	6	13
β-strand	205-210	6	13
β-strand	216-219	4	13
β-strand	224-229	6	13
β-strand	239-244	6	14
β-strand	250-255	6	14
β-strand	260-264	5	14
α-helix	268-279	12
α-helix	288-289	2
β-strand	292-294	3	13
β-strand	299-301	3	14
β-strand	311-315	5	15
β-strand	318-323	6	15
β-strand	327-333	7	15
α-helix	340-342	3
β-strand	350-356	7	15
β-strand	368-370	3	16
β-strand	376-380	5	16
β-strand	386-390	5	16
β-strand	402-404	3	16
β-strand	413-418	6	1
β-strand	424-429	6	1
β-strand	433-439	7	1

Chain C: 8 helices, 2 β-strands

Element	Residues	Length	Sheet
β-strand	566	1	9
β-strand	573	1	9
α-helix	576-578	3
α-helix	590-601	12
α-helix	610-624	15
α-helix	629-631	3
α-helix	632-642	11
α-helix	644-649	6
α-helix	653-665	13
α-helix	671-684	14

Chain D: 23 helices, 25 β-strands

Element	Residues	Length	Sheet
α-helix	12-61	50
α-helix	73	1
α-helix	75-76	2
β-strand	82-87	6	17
α-helix	91-93	3
β-strand	94-97	4	17
β-strand	99-101	3	18
α-helix	106-109	4
β-strand	114-115	2	19
β-strand	120-121	2	19
α-helix	123-125	3
β-strand	128	1	20
α-helix	135-138	4
α-helix	144-151	8
β-strand	157	1	20
α-helix	168-179	12
α-helix	223-230	8
α-helix	237-246	10
α-helix	274-284	11
β-strand	285	1	21
β-strand	292	1	21
α-helix	335-343	9
α-helix	426-428	3
α-helix	434-447	14
α-helix	451-458	8
α-helix	463-475	13
α-helix	535-538	4
β-strand	543	1	22
β-strand	556	1	22
α-helix	572-575	4
β-strand	578	1	23
α-helix	605-608	4
β-strand	614-618	5	24
β-strand	624-628	5	24
β-strand	632	1	25
β-strand	637-641	5	23
β-strand	643-646	4	19
α-helix	650-660	11
β-strand	666-668	3	19
β-strand	674-681	8	19
α-helix	683-686	4
α-helix	687	1
β-strand	688-689	2	26
β-strand	695-702	8	23
β-strand	705-712	8	23
β-strand	716	1	25
β-strand	720-722	3	24
β-strand	723-724	2	26

Chain E: 3 helices, 31 β-strands

Element	Residues	Length	Sheet
β-strand	83-90	8	17
β-strand	96-101	6	18
α-helix	106	1
β-strand	112-117	6	18
β-strand	120-126	7	18
β-strand	132-140	9	18
β-strand	147-154	8	27
β-strand	161-167	7	27
β-strand	172-176	5	27
β-strand	181-186	6	27
β-strand	193-199	7	28
β-strand	202-210	9	28
β-strand	215-219	5	28
β-strand	224-229	6	28
β-strand	239-244	6	29
β-strand	250-255	6	29
β-strand	260-264	5	29
α-helix	268-279	12
α-helix	288-289	2
β-strand	292-294	3	28
β-strand	299-301	3	29
β-strand	311-315	5	30
β-strand	318-322	5	30
β-strand	327-333	7	30
β-strand	350-357	8	30
β-strand	368-370	3	31
β-strand	376-380	5	31
β-strand	386-390	5	31
β-strand	402-404	3	31
β-strand	406	1	32
β-strand	409	1	32
β-strand	416-418	3	17
β-strand	424-428	5	17
β-strand	433-438	6	17

Chain F: 7 helices, 2 β-strands

Element	Residues	Length	Sheet
β-strand	566	1	24
β-strand	573	1	24
α-helix	576-578	3
α-helix	590-601	12
α-helix	610-624	15
α-helix	631-642	12
α-helix	644-650	7
α-helix	653-665	13
α-helix	671-682	12

Chain G: 25 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	14-61	48
β-strand	81-85	5	33
β-strand	86-87	2	34
α-helix	92-93	2
β-strand	94-101	8	33
α-helix	105-109	5
β-strand	114-115	2	35
β-strand	120-121	2	35
β-strand	128	1	36
α-helix	144-151	8
β-strand	157	1	36
α-helix	168-181	14
α-helix	223-230	8
α-helix	237-247	11
α-helix	274-277	4
α-helix	279-284	6
β-strand	285	1	37
β-strand	292	1	37
α-helix	331-343	13
α-helix	426-428	3
α-helix	434-447	14
α-helix	451-458	8
α-helix	463-475	13
α-helix	477-478	2
α-helix	535-539	5
β-strand	543	1	38
β-strand	556	1	38
α-helix	572-575	4
β-strand	578	1	39
α-helix	605-608	4
α-helix	611-613	3
β-strand	614-618	5	40
β-strand	624-628	5	40
β-strand	632	1	41
β-strand	637-641	5	39
β-strand	643-646	4	35
α-helix	648-660	13
β-strand	666-668	3	35
β-strand	674-681	8	35
α-helix	683-686	4
α-helix	687	1
β-strand	688	1	42
α-helix	689	1
β-strand	695-702	8	39
β-strand	705-712	8	39
β-strand	716	1	41
α-helix	720	1
β-strand	721	1	40
α-helix	722	1
β-strand	723	1	42
β-strand	724	1	39
β-strand	727	1	43
β-strand	729	1	43

Chain H: 3 helices, 31 β-strands

Element	Residues	Length	Sheet
β-strand	82-86	5	44
β-strand	88-89	2	34
β-strand	96-101	6	33
β-strand	111-117	7	33
β-strand	120-126	7	33
β-strand	132-140	9	33
β-strand	147-155	9	45
β-strand	160-167	8	45
β-strand	172-176	5	45
β-strand	181-186	6	45
β-strand	193-198	6	46
β-strand	205-210	6	46
β-strand	215-219	5	46
β-strand	224-229	6	46
β-strand	239-244	6	47
β-strand	250-255	6	47
β-strand	260-264	5	47
α-helix	268-279	12
α-helix	288-289	2
β-strand	292-294	3	46
β-strand	299-301	3	47
β-strand	311-315	5	48
β-strand	318-322	5	48
β-strand	327-333	7	48
β-strand	350-357	8	48
β-strand	368-370	3	49
β-strand	376-380	5	49
β-strand	386-390	5	49
β-strand	402-404	3	49
β-strand	413-418	6	44
β-strand	424-429	6	44
β-strand	433	1	34
β-strand	436-439	4	44
α-helix	440	1

6 more chain groups are not listed. Open the entry in the viewer and use the sequence panel to see them.

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Histone-lysine N-methyltransferase EZH2,Histone-lysine N-methyltransferase EZH2,Histone-lysine…	A, D, G, J	protein	695	Homo sapiens	Q15910 (AlphaFold model)
Polycomb protein EED	B, E, H, K	protein	367	Homo sapiens	O75530 (AlphaFold model)
Polycomb protein SUZ12	C, F, I, L	protein	129	Homo sapiens	Q15022 (AlphaFold model)
Jarid2 K116me3	Q, R, S, T	protein	11	Homo sapiens	Q92833 (AlphaFold model)

Sequence of entity 1 (A, D, G, J), FASTA

>5LS6_1 Histone-lysine N-methyltransferase EZH2,Histone-lysine N-methyltransferase EZH2,Histone-lysine N-methyltransferase EZH2 (chains A, D, G, J)
ETSLAEEKLTMGQTGKKSEKGPVCWRKRVKSEYMRLRQLKRFRRADEVKSMFSSNRQKIL
ERTEILNQEWKQRRIQPVHILTSVSSLRGTRECSVTSDLDFPTQVIPLKTLNAVASVPIM
YSWSPLQQNFMVEDETVLHNIPYMGDEVLDQDGTFIEELIKNYDGKVHGDRECGFINDEI
FVELVNALGQYNESRPPRKFPSDKIFEAISSMFPDKGTAEELKEKYKELTQQQLPGALPP
ECTPNIDGPNAKSVQREQSLHSFHTLFCRRCFKYDCFLHPFHATPNTYKRKNTETALDNK
PCGPQCYQHLEGAKEFAAALTAERIKTPPKRPGGRRRGRLPNNSSRPSTPTINVLESKDT
DSDREAGPGKPNIEPPENVEWSGAEASMFRVLIGTYYDNFCAIARLIGTKTCRQVYEFRV
KESSIIAPAPAEDVDTPPRKKKRKHRLWAAHCRKIQLKKDGSSNHVYNYQPCDHPRQPCD
SSCPCVIAQNFCEKFCQCSSECQNRFPGCRCKAQCNTKQCPCYLAVRECDPDLCLTCGAA
DHWDSKNVSCKNCSIQRGSKKHLLLAPSDVAGWGIFIKDPVQKNEFISEYCGEIISQDEA
DRRGKVYDKYMCSFLFNLNNDFVVDATRKGNKIRFANHSVNPNCYAKVMMVNGDHRIGIF
AKRAIQTGEELFFDYRYSQADALKYVGIEREMEIP

Sequence of entity 2 (B, E, H, K), FASTA

>5LS6_2 Polycomb protein EED (chains B, E, H, K)
GSKCKYSFKCVNSLKEDHNQPLFGVQFNWHSKEGDPLVFATVGSNRVTLYECHSQGEIRL
LQSYVDADADENFYTCAWTYDSNTSHPLLAVAGSRGIIRIINPITMQCIKHYVGHGNAIN
ELKFHPRDPNLLLSVSKDHALRLWNIQTDTLVAIFGGVEGHRDEVLSADYDLLGEKIMSC
GMDHSLKLWRINSKRMMNAIKESYDYNPNKTNRPFISQKIHFPDFSTRDIHRNYVDCVRW
LGDLILSKSCENAIVCWKPGKMEDDIDKIKPSESNVTILGRFDYSQCDIWYMRFSMDFWQ
KMLALGNQVGKLYVWDLEVEDPHKAKCTTLTHHKCGAAIRQTSFSRDSSILIAVCDDASI
WRWDRLR

Sequence of entity 3 (C, F, I, L), FASTA

>5LS6_3 Polycomb protein SUZ12 (chains C, F, I, L)
GSSGHNRLYFHSDTCLPLRPQEMEVDSEDEKDPEWLREKTITQIEEFSDVNEGEKEVMKL
WNLHVMKHGFIADNQMNHACMLFVENYGQKIIKKNLCRNFMLHLVSMHDFNLISIMSIDK
AVTKLREMQ

Sequence of entity 4 (Q, R, S, T), FASTA

>5LS6_4 Jarid2 K116me3 (chains Q, R, S, T)
RLQAQRKFAQS

Ligands and cofactors

ID	Name	Formula	Copies
ZN	Zinc ion	Zn	32
74D	1-[(1~{R})-1-[1-[2,2-bis(fluoranyl)propyl]piperidin-4-yl]ethyl]-~{N}-[(4-methox…	C28 H36 F2 N4 O3	4

Primary citation

Identification of (R)-N-((4-Methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide (CPI-1205), a Potent and Selective Inhibitor of Histone Methyltransferase EZH2, Suitable for Phase I Clinical Trials for B-Cell…. Vaswani, R.G., Gehling, V.S., Dakin, L.A. et al. J Med Chem (2016) 59:9928-9941. DOI 10.1021/acs.jmedchem.6b01315 · PubMed

Other PDB entries of the same protein (UniProt Q15910 (AlphaFold model), which also has an AlphaFold model), best resolution first:

5U5T 1.6 Å, Crystal structure of EED in complex with H3K27Me3 peptide and…
7QK4 1.6 Å, EED in complex with PRC2 allosteric inhibitor compound 22 (MAK683)
7QJG 1.8 Å, EED in complex with PRC2 allosteric inhibitor compound 6
7QJU 1.8 Å, EED in complex with PRC2 allosteric inhibitor compound 7
5H14 1.9 Å, EED in complex with an allosteric PRC2 inhibitor EED666
5H19 1.9 Å, EED in complex with PRC2 allosteric inhibitor EED162
5U62 1.9 Å, Crystal structure of EED in complex with H3K27Me3 peptide and…
4MI0 2.0 Å, Human Enhancer of Zeste (Drosophila) Homolog 2(EZH2)
4MI5 2.0 Å, Crystal structure of the EZH2 SET domain
5WUK 2.03 Å, Crystal structure of EED [G255D] in complex with EZH2 peptide and EED226 compound
6LO2 2.21 Å, Crystal structure of EED in complex with EZH2 peptide and compound 11#
5H15 2.27 Å, EED in complex with PRC2 allosteric inhibitor EED709

Browse structure collections

About this viewer

MolViewer shows 5LS6 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.