6B3W: Hs/AcPRC2

Structure of Hs/AcPRC2 in complex with 5,8-dichloro-7-(3,5-dimethyl-1,2-oxazol-4-yl)-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-3,4-dihydroisoquinolin-1(2H)-one. Determined by X-ray diffraction at 3.05 Å resolution. Released 27 Dec 2017.

Method: X-ray diffraction
Resolution: 3.05 Å
Organisms: Anolis carolinensis, Homo sapiens
Chains: 6
Atoms: 15,564
Mol. weight: 275.78 kDa
Ligands: CJG, ZN
Released: 27 Dec 2017

Explore 6B3W in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

6B3W contains 66 α-helices and 118 β-strands across 6 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: 21 helices, 27 β-strands

Element	Residues	Length	Sheet
α-helix	12-62	51
β-strand	65	1	1
α-helix	66-68	3
β-strand	82-85	4	2
α-helix	91-93	3
β-strand	94-97	4	2
β-strand	99-101	3	3
α-helix	102-103	2
β-strand	114-115	2	4
β-strand	120-121	2	5
α-helix	168-184	17
α-helix	209-218	10
α-helix	225-231	7
α-helix	267-271	5
β-strand	273-274	2	6
β-strand	279-280	2	6
α-helix	288-290	3
α-helix	291-294	4
α-helix	335-348	14
α-helix	352-359	8
α-helix	366-372	7
α-helix	415-417	3
α-helix	432-435	4
β-strand	440	1	7
β-strand	453	1	7
β-strand	462	1	8
α-helix	469-472	4
β-strand	475	1	9
β-strand	498	1	8
α-helix	508-510	3
β-strand	511-515	5	10
β-strand	521-525	5	10
β-strand	529	1	11
β-strand	534-538	5	9
β-strand	541-544	4	5
α-helix	545-556	12
β-strand	563-565	3	5
β-strand	570-573	4	5
β-strand	577-578	2	4
α-helix	580-583	4
α-helix	584	1
β-strand	585-586	2	12
β-strand	592-598	7	9
β-strand	603-609	7	9
β-strand	613	1	11
β-strand	618	1	10
β-strand	620-621	2	12
α-helix	625-627	3

Chain B: 23 helices, 26 β-strands

Element	Residues	Length	Sheet
α-helix	12-60	49
α-helix	66-68	3
β-strand	82-85	4	13
α-helix	91-93	3
β-strand	94-97	4	13
β-strand	99-101	3	14
α-helix	102-103	2
β-strand	114-115	2	15
β-strand	120-121	2	16
α-helix	168-184	17
α-helix	209-218	10
α-helix	225-234	10
α-helix	267-271	5
β-strand	273-274	2	17
β-strand	279-280	2	17
α-helix	288-290	3
α-helix	291-294	4
α-helix	335-348	14
α-helix	352-359	8
α-helix	366-372	7
α-helix	415-417	3
α-helix	432-435	4
β-strand	440	1	18
β-strand	453	1	18
β-strand	462	1	19
α-helix	469-472	4
β-strand	475	1	20
β-strand	498	1	19
α-helix	508-510	3
β-strand	511-515	5	21
β-strand	521-525	5	21
β-strand	529	1	22
β-strand	534-537	4	20
β-strand	541-544	4	16
α-helix	545-556	12
β-strand	563-565	3	16
β-strand	570-573	4	16
β-strand	577-578	2	15
α-helix	580-583	4
α-helix	584	1
β-strand	585-586	2	20
β-strand	592-599	8	20
β-strand	602-609	8	20
β-strand	613	1	22
α-helix	617	1
β-strand	618	1	21
α-helix	619	1
β-strand	620-621	2	20
α-helix	625-627	3

Chain E: 5 helices, 30 β-strands

Element	Residues	Length	Sheet
β-strand	69-75	7	23
β-strand	76	1	13
β-strand	82-87	6	14
α-helix	91-92	2
β-strand	97-103	7	14
β-strand	106-112	7	14
α-helix	114-116	3
β-strand	118-126	9	14
β-strand	133-140	8	24
β-strand	147-153	7	24
β-strand	157-162	6	24
β-strand	167-173	7	24
β-strand	179-184	6	25
β-strand	191-196	6	25
β-strand	201-205	5	25
β-strand	210-215	6	25
β-strand	225-230	6	26
β-strand	236-241	6	26
β-strand	246-250	5	26
α-helix	254-265	12
α-helix	268-270	3
β-strand	278-280	3	25
β-strand	285-287	3	26
β-strand	297-301	5	27
β-strand	304-308	5	27
β-strand	313-319	7	27
β-strand	336-343	8	27
β-strand	354-356	3	28
β-strand	362-366	5	28
β-strand	372-376	5	28
β-strand	387-390	4	28
α-helix	398	1
β-strand	399-404	6	23
β-strand	410-415	6	23
β-strand	419-424	6	23

Chain F: 5 helices, 31 β-strands

Element	Residues	Length	Sheet
β-strand	69-75	7	29
β-strand	76	1	2
β-strand	82-87	6	3
β-strand	91	1	1
α-helix	92	1
β-strand	97-103	7	3
β-strand	106-112	7	3
α-helix	114-116	3
β-strand	118-126	9	3
β-strand	133-140	8	30
β-strand	147-153	7	30
β-strand	157-162	6	30
β-strand	167-173	7	30
β-strand	179-184	6	31
β-strand	191-196	6	31
β-strand	201-205	5	31
β-strand	210-215	6	31
β-strand	225-230	6	32
β-strand	236-241	6	32
β-strand	246-250	5	32
α-helix	254-265	12
α-helix	268-270	3
β-strand	278-280	3	31
β-strand	285-287	3	32
β-strand	297-301	5	33
β-strand	304-308	5	33
β-strand	313-319	7	33
β-strand	336-343	8	33
β-strand	354-356	3	34
β-strand	362-366	5	34
β-strand	372-376	5	34
β-strand	386-390	5	34
α-helix	398	1
β-strand	399-404	6	29
β-strand	410-415	6	29
β-strand	419-424	6	29

Chains S and T: 6 helices, 2 β-strands

Element	Residues	Length	Sheet
β-strand	566	1	21
β-strand	573	1	21
α-helix	590-601	12
α-helix	608-624	17
α-helix	629-631	3
α-helix	632-649	18
α-helix	653-665	13
α-helix	673-685	13

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Enhancer of zeste 2 polycomb repressive complex 2 subunit,Enhancer of zeste 2 polycomb repressive…	A, B	protein	643	Anolis carolinensis	G1KPH4 (AlphaFold model)
Polycomb protein EED	E, F	protein	362	Homo sapiens	O75530 (AlphaFold model)
Polycomb protein SUZ12	S, T	protein	191	Homo sapiens	Q15022 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>6B3W_1 Enhancer of zeste 2 polycomb repressive complex 2 subunit,Enhancer of zeste 2 polycomb repressive complex 2 subunit (chains A, B)
MGQTGKKSEKGPICWRKRVKSEYMRLRQLKRFRRADEVKSMFNSNRQKIQERTEILNQEW
KQRRIQPVHIMTSVSSLRGTRECSVTSDLDFPKQVIPLKTLNAVASVPIMYSWSPLQQNF
MVEDETVLHNIPYMGDEVLDQDGTFIEELIKNYDGKVHGDRECGFINDEIFVELVNALGQ
LDRRDEKQKNQESNQIDKESHPPRKFPSDKIFEAISSMFPDKGTAEELKEKYKELTEQQL
PGALPPECTPNIDGPNAKSVQREQSLHSFHTLFCRRCFKYDCFLHPFHATPNTYKRKNTE
MAIDNKPCGPHCYQHLEGAKEFAAALTAENVEWSGAEASMFRVLIGTYYDNFCAIARLIG
TKTCRQVYEFRVKESSIIAPAPAEDVDTLGGGGSGGGGSGGGGSAAADGSSNHVYNYQPC
DHPRQPCDNSCPCVIAQNFCEKFCQCSSECQNRFPGCRCKAQCNTKQCPCYLAVRECDPD
LCLTCGAADHWDSKNVSCKNCSIQRGSKKHLLLAPSDVAGWGIFIKDPVQKNEFISEYCG
EIISQDEADRRGKVYDKYMCSFLFNLNNDFVVDATRKGNKIRFANHSVNPNCYAKVMMVN
GDHRIGIFAKRAIQTGEELFFDYRYSQADALKYVGIEREMEIP

Sequence of entity 2 (E, F), FASTA

>6B3W_2 Polycomb protein EED (chains E, F)
MSFKCVNSLKEDHNQPLFGVQFNWHSKEGDPLVFATVGSNRVTLYECHSQGEIRLLQSYV
DADADENFYTCAWTYDSNTSHPLLAVAGSRGIIRIINPITMQCIKHYVGHGNAINELKFH
PRDPNLLLSVSKDHALRLWNIQTDTLVAIFGGVEGHRDEVLSADYDLLGEKIMSCGMDHS
LKLWRINSKRMMNAIKESYDYNPNKTNRPFISQKIHFPDFSTRDIHRNYVDCVRWLGDLI
LSKSCENAIVCWKPGKMEDDIDKIKPSESNVTILGRFDYSQCDIWYMRFSMDFWQKMLAL
GNQVGKLYVWDLEVEDPHKAKCTTLTHHKCGAAIRQTSFSRDSSILIAVCDDASIWRWDR
LR

Sequence of entity 3 (S, T), FASTA

>6B3W_3 Polycomb protein SUZ12 (chains S, T)
MDYKDDDDKGESEDGEVEQQRTYSSGHNRLYFHSDTCLPLRPQEMEVDDEDEKDPEWLRE
KTITQIEEFSDVNEGEKEVMKLWNLHVMKHGFIADNQMNHACMLFVENYGQKIIKKNLCR
NFMLHLVSMHDFNLISIMSIDKAVTKLREMQQKLEKGESASPANEEITEEQNGTANGFSE
INSKEKALETD

Ligands and cofactors

ID	Name	Formula	Copies
CJG	5,8-dichloro-7-(3,5-dimethyl-1,2-oxazol-4-yl)-2-[(4,6-dimethyl-2-oxo-1,2-dihydr…	C22 H21 Cl2 N3 O3	2
ZN	Zinc ion	Zn	14

Primary citation

Optimization of Orally Bioavailable Enhancer of Zeste Homolog 2 (EZH2) Inhibitors Using Ligand and Property-Based Design Strategies: Identification of Development Candidate (R)-5,8-Dichloro-7-(methoxy(oxetan-3-yl)methyl)-2-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3,4-dihydroisoqui…. Kung, P.P., Bingham, P., Brooun, A. et al. J Med Chem (2018) 61:650-665. DOI 10.1021/acs.jmedchem.7b01375 · PubMed

Other PDB entries of the same protein (UniProt G1KPH4 (AlphaFold model), which also has an AlphaFold model), best resolution first:

5IJ7 2.62 Å, Structure of Hs/AcPRC2 in complex with a pyridone inhibitor
4W2R 2.81 Å, Structure of Hs/AcPRC2 in complex with 5,8-dichloro-2-[(4-methoxy-6-methyl-2-oxo-1,2-dihy…
5IJ8 2.99 Å, Structure of the primary oncogenic mutant Y641N Hs/AcPRC2 in complex with a pyridone…

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