7JTO: Protac MS33

Crystal structure of Protac MS33 in complex with the WD repeat-containing protein 5 and pVHL:ElonginC:ElonginB. Determined by X-ray diffraction at 1.7 Å resolution. Released 6 Oct 2021.

Method: X-ray diffraction
Resolution: 1.7 Å
Organism: Homo sapiens
Chains: 4
Atoms: 5,804
Mol. weight: 77.33 kDa
Ligands: VKA, SCN
Released: 6 Oct 2021

Explore 7JTO in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7JTO contains 20 α-helices and 57 β-strands across 4 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 B: 1 helix, 28 β-strands

Element	Residues	Length	Sheet
β-strand	36-41	6	1
β-strand	48-53	6	2
β-strand	59-64	6	2
β-strand	68-73	6	2
β-strand	79-84	6	2
β-strand	90-95	6	3
β-strand	101-106	6	3
β-strand	111-115	5	3
β-strand	120-125	6	3
β-strand	132-137	6	4
β-strand	143-148	6	4
β-strand	153-157	5	4
β-strand	163-167	5	4
β-strand	174-179	6	5
β-strand	185-190	6	5
β-strand	195-199	5	5
β-strand	205-209	5	5
α-helix	215-216	2
β-strand	217-222	6	6
β-strand	228-233	6	6
β-strand	237-242	6	6
β-strand	247-252	6	6
β-strand	264-267	4	7
β-strand	273-277	5	7
β-strand	283-287	5	7
β-strand	293-297	5	7
β-strand	304-309	6	1
β-strand	315-320	6	1
β-strand	327-331	5	1

Chain J: 8 helices, 13 β-strands

Element	Residues	Length	Sheet
β-strand	2-9	8	8
β-strand	10	1	9
β-strand	12-19	8	8
β-strand	23	1	10
α-helix	24-35	12
α-helix	39-41	3
β-strand	42-46	5	8
β-strand	49-50	2	8
α-helix	51-52	2
β-strand	56	1	10
α-helix	57-60	4
β-strand	68	1	11
β-strand	71	1	11
α-helix	72	1
β-strand	73-79	7	8
β-strand	80-81	2	12
β-strand	84-85	2	12
α-helix	86-88	3
β-strand	90	1	9
α-helix	91-94	4
α-helix	96-100	5

Chain K: 4 helices, 3 β-strands

Element	Residues	Length	Sheet
β-strand	18-22	5	8
β-strand	28-32	5	8
α-helix	33-36	4
α-helix	40-46	7
β-strand	59-61	3	8
α-helix	67-83	17
α-helix	97-110	14

Chain L: 7 helices, 13 β-strands

Element	Residues	Length	Sheet
α-helix	59-61	3
β-strand	71-78	8	13
α-helix	83	1
β-strand	84-89	6	14
β-strand	95-97	3	14
β-strand	101	1	14
β-strand	106-112	7	13
β-strand	116-121	6	14
β-strand	127	1	14
β-strand	129-130	2	13
β-strand	133	1	13
β-strand	136	1	14
β-strand	142	1	15
β-strand	145	1	15
α-helix	146	1
β-strand	147-152	6	13
α-helix	158-169	12
α-helix	172-177	6
α-helix	182-189	8
α-helix	194-204	11

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
WD repeat-containing protein 5	B	protein	308	Homo sapiens	P61964 (AlphaFold model)
Elongin-B	J	protein	104	Homo sapiens	Q15370 (AlphaFold model)
Elongin-C	K	protein	97	Homo sapiens	Q15369 (AlphaFold model)
von Hippel-Lindau disease tumor suppressor	L	protein	162	Homo sapiens	P40337 (AlphaFold model)

Sequence of entity 1 (B), FASTA

>7JTO_1 WD repeat-containing protein 5 (chains B)
EFHMVKPNYALKFTLAGHTKAVSSVKFSPNGEWLASSSADKLIKIWGAYDGKFEKTISGH
KLGISDVAWSSDSNLLVSASDDKTLKIWDVSSGKCLKTLKGHSNYVFCCNFNPQSNLIVS
GSFDESVRIWDVKTGKCLKTLPAHSDPVSAVHFNRDGSLIVSSSYDGLCRIWDTASGQCL
KTLIDDDNPPVSFVKFSPNGKYILAATLDNTLKLWDYSKGKCLKTYTGHKNEKYCIFANF
SVTGGKWIVSGSEDNLVYIWNLQTKEIVQKLQGHTDVVISTACHPTENIIASAALENDKT
IKLWKSDC

Sequence of entity 2 (J), FASTA

>7JTO_2 Elongin-B (chains J)
MDVFLMIRRHKTTIFTDAKESSTVFELKRIVEGILKRPPDEQRLYKDDQLLDDGKTLGEC
GFTSQTARPQAPATVGLAFRADDTFEALCIEPFSSPPELPDVMK

Sequence of entity 3 (K), FASTA

>7JTO_3 Elongin-C (chains K)
MMYVKLISSDGHEFIVKREHALTSGTIKAMLSGPGQFAENETNEVNFREIPSHVLSKVCM
YFTYKVRYTNSSTEIPEFPIAPEIALELLMAANFLDC

Sequence of entity 4 (L), FASTA

>7JTO_4 von Hippel-Lindau disease tumor suppressor (chains L)
GSMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHS
YRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVK
PENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD

Ligands and cofactors

ID	Name	Formula	Copies
VKA	3-methyl-N-(11-{[2-(4-{[4'-(4-methylpiperazin-1-yl)-3'-{[6-oxo-4-(trifluorometh…	C64 H84 F3 N11 O7 S	1
SCN	Thiocyanate ion	C N S	4

Water and common crystallization additives (NA, GOL, EDO) are not listed.

Primary citation

A selective WDR5 degrader inhibits acute myeloid leukemia in patient-derived mouse models. Yu, X., Li, D., Kottur, J. et al. Sci Transl Med (2021) 13:eabj1578-eabj1578. DOI 10.1126/scitranslmed.abj1578 · PubMed

Other PDB entries of the same protein (UniProt P61964 (AlphaFold model), which also has an AlphaFold model), best resolution first:

6E1Z 1.1 Å, Displacement of WDR5 from chromatin by a pharmacological WIN site inhibitor with…
6U6W 1.2 Å, Discovery and optimization of salicyclic acid-derived sulfonamide inhibitors of the…
6E1Y 1.22 Å, Discovery of Potent 2-Aryl-6,7-Dihydro-5HPyrrolo[ 1,2-a]imidazoles as WDR5 WIN-site…
6UHZ 1.26 Å, WDR5 in complex with Myc site fragment inhibitor
6UHY 1.26 Å, WDR5 in complex with Myc site fragment inhibitor
7BED 1.26 Å, X-ray structure of WDR5 bound to the WDR5 win motif peptide
6U8B 1.26 Å, Discovery and optimization of salicyclic acid-derived sulfonamide inhibitors of the…
24XP 1.3 Å, Crystal structure of WDR5 F133A variant in complex with MBD3C
4ERY 1.3 Å, X-ray structure of WDR5-MLL3 Win motif peptide binary complex
8G3E 1.33 Å, Crystal structure of human WDR5 in complex with (1M)-N-[(3,5-difluoro[1,1'-biphenyl]-4-yl…
3EMH 1.37 Å, Structural basis of WDR5-MLL interaction
3UVK 1.4 Å, Crystal structure of WDR5 in complex with the WDR5-interacting motif of MLL2

Browse structure collections

About this viewer

MolViewer shows 7JTO 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.