8ROY: Human DDB1-DDA1-DCAF15 E3 ubiquitin ligase

Name: PDB 8ROY: Structure of the human DDB1-DDA1-DCAF15 E3 ubiquitin ligase bound to compound furan 24
Published: 2024-04-03
License: https://creativecommons.org/publicdomain/zero/1.0/
Keywords: ligase

Structure of the human DDB1-DDA1-DCAF15 E3 ubiquitin ligase bound to compound furan 24. Determined by electron microscopy at 3.1 Å resolution. Released 3 Apr 2024.

Method: Electron microscopy
Resolution: 3.1 Å
Organism: Homo sapiens
Chains: 3
Atoms: 8,294
Mol. weight: 172.54 kDa
Ligands: A1H18
Released: 3 Apr 2024

Explore 8ROY in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8ROY contains 23 α-helices and 109 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: 8 helices, 27 β-strands

Element	Residues	Length	Sheet
α-helix	37-46	10
α-helix	51-54	4
β-strand	61-63	3	1
β-strand	79-83	5	2
β-strand	89-93	5	2
β-strand	109-113	5	2
α-helix	119-120	2
β-strand	121-126	6	2
β-strand	140-144	5	3
β-strand	151-157	7	3
β-strand	178-186	9	3
α-helix	187-189	3
β-strand	217	1	3
β-strand	219-224	6	3
α-helix	228-230	3
α-helix	233-236	4
β-strand	242-244	3	4
β-strand	250	1	5
β-strand	253-255	3	4
β-strand	258	1	6
β-strand	420-421	2	3
β-strand	441	1	6
β-strand	446	1	4
β-strand	449	1	5
α-helix	450-460	11
β-strand	474-482	9	7
β-strand	487-494	8	7
β-strand	514	1	8
β-strand	515-522	8	7
β-strand	529-534	6	7
β-strand	538	1	8
α-helix	548-561	14
β-strand	574-576	3	3
β-strand	590-591	2	1
β-strand	596-598	3	1

Chain B: 13 helices, 80 β-strands

Element	Residues	Length	Sheet
β-strand	4-10	7	9
β-strand	18-21	4	10
β-strand	30-33	4	10
β-strand	39-43	5	10
β-strand	50-55	6	10
β-strand	61-67	7	11
β-strand	76-81	6	11
β-strand	87-94	8	11
β-strand	97-105	9	11
α-helix	114	1
β-strand	115	1	12
α-helix	116	1
β-strand	121-124	4	12
β-strand	130-136	7	12
β-strand	139-144	6	12
β-strand	151-154	4	11
β-strand	155	1	12
β-strand	158	1	12
β-strand	166-169	4	13
β-strand	177-183	7	13
β-strand	188-194	7	13
β-strand	196	1	14
β-strand	201	1	14
β-strand	204	1	13
β-strand	210-211	2	13
β-strand	216-221	6	15
β-strand	229-233	5	15
β-strand	236-241	6	15
β-strand	244-248	5	15
α-helix	252-255	4
β-strand	258-263	6	16
β-strand	270-275	6	16
β-strand	279-286	8	16
β-strand	289	1	17
β-strand	295	1	17
β-strand	299-307	9	16
α-helix	310-311	2
β-strand	313-316	4	18
α-helix	318-320	3
β-strand	321	1	19
β-strand	322-325	4	18
β-strand	331-332	2	18
β-strand	335-336	2	19
α-helix	340-341	2
β-strand	347-348	2	19
β-strand	352-353	2	18
β-strand	362-365	4	20
β-strand	374-377	4	20
β-strand	379	1	20
β-strand	386-390	5	20
β-strand	712-716	5	20
β-strand	720-727	8	21
β-strand	732-741	10	21
β-strand	751	1	21
β-strand	762-765	4	21
β-strand	786-795	10	21
β-strand	801-806	6	21
α-helix	807-808	2
β-strand	811-819	9	22
β-strand	828-835	8	22
β-strand	846-854	9	22
β-strand	857-864	8	22
β-strand	872	1	23
β-strand	875-876	2	24
β-strand	879-880	2	24
β-strand	883-884	2	23
β-strand	887-888	2	23
β-strand	889-893	5	24
β-strand	899-904	6	24
β-strand	911-917	7	25
β-strand	920-925	6	25
β-strand	930-934	5	25
β-strand	935-936	2	26
β-strand	941-942	2	26
β-strand	946-947	2	25
β-strand	954-959	6	27
β-strand	964-969	6	27
β-strand	974-979	6	27
α-helix	986-989	4
β-strand	991	1	25
β-strand	992-998	7	27
β-strand	1004-1009	6	9
β-strand	1027-1032	6	9
β-strand	1037-1042	6	9
α-helix	1045-1061	17
α-helix	1070-1074	5
β-strand	1076-1077	2	28
β-strand	1082-1083	2	28
β-strand	1086	1	27
β-strand	1088-1090	3	9
α-helix	1091-1096	6
α-helix	1102-1108	7
α-helix	1127-1137	11

Chain D: 2 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	31-33	3
β-strand	34-35	2	10
β-strand	45-49	5	11
α-helix	54-67	14

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
DDB1- and CUL4-associated factor 15	A	protein	603	Homo sapiens	Q66K64 (AlphaFold model)
DNA damage-binding protein 1	B	protein	836	Homo sapiens	Q16531 (AlphaFold model)
DET1- and DDB1-associated protein 1	D	protein	102	Homo sapiens	Q9BW61 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>8ROY_1 DDB1- and CUL4-associated factor 15 (chains A)
GSHMAPSSKSERNSGAGSGGGGPGGAGGKRAAGRRREHVLKQLERVKISGQLSPRLFRKL
PPRVCVSLKNIVDEDFLYAGHIFLGFSKCGRYVLSYTSSSGDDDFSFYIYHLYWWEFNVH
SKLKLVRQVRLFQDEEIYSDLYLTVCEWPSDASKVIVFGFNTRSANGMLMNMMMMSDENH
RDIYVSTVAVPPPGRCAACQDASRAHPGDPNAQCLRHGFMLHTKYQVVYPFPTFQPAFQL
KKDQVVLLNTSYSLVACAVSVHSAGDRSFCQILYDHSTCPLAPASPPEPQSPELPPALPS
FCPEAAPARSSGSPEPSPAIAKAKEFVADIFRRAKEAKGGVPEEARPALCPGPSGSRCRA
HSEPLALCGETAPRDSPPASEAPASEPGYVNYTKLYYVLESGEGTEPEDELEDDKISLPF
VVTDLRGRNLRPMRERTAVQGQYLTVEQLTLDFEYVINEVIRHDATWGHQFCSFSDYDIV
ILEVCPETNQVLINIGLLLLAFPSPTEEGQLRPKTYHTSLKVAWDLNTGIFETVSVGDLT
EVKGQTSGSVWSSYRKSCVDMVMKWLVPESSGRYVNRMTNEALHKGCSLKVLADSERYTW
IVL

Sequence of entity 2 (B), FASTA

>8ROY_2 DNA damage-binding protein 1 (chains B)
MSYNYVVTAQKPTAVNGCVTGHFTSAEDLNLLIAKNTRLEIYVVTAEGLRPVKEVGMYGK
IAVMELFRPKGESKDLLFILTAKYNACILEYKQSGESIDIITRAHGNVQDRIGRPSETGI
IGIIDPECRMIGLRLYDGLFKVIPLDRDNKELKAFNIRLEELHVIDVKFLYGCQAPTICF
VYQDPQGRHVKTYEVSLREKEFNKGPWKQENVEAEASMVIAVPEPFGGAIIIGQESITYH
NGDKYLAIAPPIIKQSTIVCHNRVDPNGSRYLLGDMEGRLFMLLLEKEEQMDGTVTLKDL
RVELLGETSIAECLTYLDNGVVFVGSRLGDSQLVKLNVDSNEQGSYVVAMETFTNLGPIV
DMCVVDLERQGQGQLVTCSGAFKEGSLRIIRNGIGGNGNSGEIQKLHIRTVPLYESPRKI
CYQEVSQCFGVLSSRIEVQDTSGGTTALRPSASTQALSSSVSSSKLFSSSTAPHETSFGE
EVEVHNLLIIDQHTFEVLHAHQFLQNEYALSLVSCKLGKDPNTYFIVGTAMVYPEEAEPK
QGRIVVFQYSDGKLQTVAEKEVKGAVYSMVEFNGKLLASINSTVRLYEWTTEKELRTECN
HYNNIMALYLKTKGDFILVGDLMRSVLLLAYKPMEGNFEEIARDFNPNWMSAVEILDDDN
FLGAENAFNLFVCQKDSAATTDEERQHLQEVGLFHLGEFVNVFCHGSLVMQNLGETSTPT
QGSVLFGTVNGMIGLVTSLSESWYNLLLDMQNRLNKVIKSVGKIEHSFWRSFHTERKTEP
ATGFIDGDLIESFLDISRPKMQEVVANLQYDDGSGMKREATADDLIKVVEELTRIH

Sequence of entity 3 (D), FASTA

>8ROY_3 DET1- and DDB1-associated protein 1 (chains D)
MADFLKGLPVYNKSNFSRFHADSVCKASNRRPSVYLPTREYPSEQIIVTEKTNILLRYLH
QQWDKKNAAKKRDQEQVELEGESSAPPRKVARTDSPDMHEDT

Ligands and cofactors

ID	Name	Formula	Copies
A1H18	1-[5-[[3,4-bis(chloranyl)-1~{H}-indol-7-yl]sulfamoyl]-3-methyl-furan-2-yl]carbo…	C21 H22 Cl2 N4 O5 S	1

Primary citation

Optimization of Potent Ligands for the E3 Ligase DCAF15 and Evaluation of Their Use in Heterobifunctional Degraders. Lucas, S.C.C., Ahmed, A., Ashraf, S.N. et al. J Med Chem (2024) 67:5538-5566. DOI 10.1021/acs.jmedchem.3c02136 · PubMed

Other PDB entries of the same protein (UniProt Q66K64 (AlphaFold model), which also has an AlphaFold model), best resolution first:

6UD7 2.3 Å, Crystal structure of full-length human DCAF15-DDB1(deltaBPB)-DDA1-RBM39 in complex with…
6UE5 2.61 Å, Crystal structure of full-length human DCAF15-DDB1-deltaPBP-DDA1-RBM39 in complex with…
6PAI 2.9 Å, Structure of the human DDB1-DDA1-DCAF15 E3 ubiquitin ligase bound to RBM39 and…
6Q0R 2.9 Å, Structure of DDB1-DDA1-DCAF15 complex bound to E7820 and RBM39
6Q0V 2.9 Å, Structure of DDB1-DDA1-DCAF15 complex bound to tasisulam and RBM39
6Q0W 2.9 Å, Structure of DDB1-DDA1-DCAF15 complex bound to Indisulam and RBM39
8ROX 3.3 Å, Structure of the human DDB1-DDA1-DCAF15 E3 ubiquitin ligase bound to compound furan 12
6SJ7 3.54 Å, Structure of the human DDB1-DDA1-DCAF15 E3 ubiquitin ligase bound to RBM39 and Indisulam

Browse structure collections

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