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

Name: PDB 8ROX: Structure of the human DDB1-DDA1-DCAF15 E3 ubiquitin ligase bound to compound furan 12
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 12. Determined by electron microscopy at 3.3 Å resolution. Released 3 Apr 2024.

Method: Electron microscopy
Resolution: 3.3 Å
Organism: Homo sapiens
Chains: 3
Atoms: 7,249
Mol. weight: 172.44 kDa
Ligands: A1H17
Released: 3 Apr 2024

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

Secondary structure: helices and β-sheets

8ROX contains 27 α-helices and 99 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: 11 helices, 20 β-strands

Element	Residues	Length	Sheet
α-helix	36-46	11
α-helix	58-59	2
β-strand	79-83	5	1
β-strand	89-93	5	1
β-strand	109-113	5	1
β-strand	121-126	6	1
β-strand	138-144	7	2
β-strand	151-158	8	2
β-strand	178-186	9	2
α-helix	187-189	3
α-helix	210-213	4
β-strand	217-224	8	2
α-helix	228-230	3
α-helix	233-236	4
β-strand	243-246	4	3
β-strand	250-258	9	3
β-strand	420-423	4	2
β-strand	424	1	4
β-strand	427	1	4
β-strand	441-449	9	3
α-helix	450-460	11
α-helix	463-467	5
β-strand	476-482	7	5
β-strand	487-492	6	5
β-strand	517-522	6	5
β-strand	529-531	3	5
α-helix	545-561	17
α-helix	565	1
β-strand	566	1	6
α-helix	567	1
β-strand	574-575	2	2

Chain B: 14 helices, 77 β-strands

Element	Residues	Length	Sheet
β-strand	4-10	7	7
β-strand	17-21	5	8
β-strand	30-35	6	8
β-strand	38-44	7	8
β-strand	49-55	7	8
β-strand	61-67	7	9
β-strand	76-81	6	9
β-strand	85-92	8	9
β-strand	99-107	9	9
β-strand	113	1	6
β-strand	115	1	10
α-helix	119-120	2
β-strand	121-124	4	11
β-strand	130-134	5	11
β-strand	136	1	10
β-strand	140-144	5	11
β-strand	151-154	4	9
β-strand	155-157	3	11
β-strand	164-169	6	12
β-strand	177-182	6	12
β-strand	189-196	8	12
β-strand	201-204	4	12
β-strand	210-211	2	12
β-strand	216-221	6	13
α-helix	222-223	2
β-strand	229-233	5	13
β-strand	236-240	5	13
β-strand	241	1	14
β-strand	243	1	14
β-strand	246-248	3	13
α-helix	251-254	4
β-strand	258-263	6	15
β-strand	270-275	6	15
β-strand	279-285	7	15
β-strand	288	1	16
β-strand	296	1	16
β-strand	300-307	8	15
α-helix	310-311	2
β-strand	313	1	17
β-strand	316-317	2	18
β-strand	321-324	4	18
β-strand	325	1	17
β-strand	331-336	6	18
α-helix	340-341	2
β-strand	347-353	7	18
β-strand	361-365	5	19
β-strand	374-379	6	19
α-helix	382-384	3
β-strand	386-391	6	19
β-strand	711-716	6	19
β-strand	720-727	8	20
β-strand	732-740	9	20
β-strand	741-743	3	21
β-strand	749-751	3	21
α-helix	756-759	4
β-strand	762-765	4	20
β-strand	787-795	9	20
β-strand	801-806	6	20
β-strand	811-819	9	22
β-strand	828-835	8	22
β-strand	845-854	10	22
β-strand	857-867	11	22
β-strand	870	1	23
β-strand	874-876	3	24
β-strand	879-881	3	24
β-strand	884	1	23
β-strand	890-893	4	24
β-strand	899-901	3	24
β-strand	911-917	7	25
β-strand	920-925	6	25
β-strand	930-933	4	25
β-strand	947	1	25
β-strand	956-961	6	26
β-strand	964-968	5	26
β-strand	974-979	6	26
α-helix	988-990	3
β-strand	991	1	25
β-strand	992-998	7	26
β-strand	1004-1009	6	7
β-strand	1028-1032	5	7
β-strand	1037-1042	6	7
α-helix	1045-1061	17
α-helix	1065-1067	3
α-helix	1070-1074	5
β-strand	1076-1077	2	27
β-strand	1082-1083	2	27
β-strand	1086	1	26
β-strand	1088-1089	2	7
α-helix	1092-1099	8
α-helix	1102-1109	8
α-helix	1127-1136	10

Chain D: 2 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	32	1
β-strand	33-34	2	8
β-strand	45-49	5	9
α-helix	54-66	13

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

>8ROX_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

>8ROX_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

>8ROX_3 DET1- and DDB1-associated protein 1 (chains D)
MADFLKGLPVYNKSNFSRFHADSVCKASNRRPSVYLPTREYPSEQIIVTEKTNILLRYLH
QQWDKKNAAKKRDQEQVELEGESSAPPRKVARTDSPDMHEDT

Ligands and cofactors

ID	Name	Formula	Copies
A1H17	5-[[3,4-bis(chloranyl)-1~{H}-indol-7-yl]sulfamoyl]-~{N},~{N},3-trimethyl-furan-…	C16 H15 Cl2 N3 O4 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
8ROY 3.1 Å, Structure of the human DDB1-DDA1-DCAF15 E3 ubiquitin ligase bound to compound furan 24
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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