6ZHC: Von Hippel-Lindau disease tumor suppressor

PROTAC6 mediated complex of VHL:EloB:EloC and Bcl-xL. Determined by X-ray diffraction at 1.92 Å resolution. Released 5 Aug 2020.

Method: X-ray diffraction
Resolution: 1.92 Å
Organism: Homo sapiens
Chains: 4
Atoms: 4,810
Mol. weight: 70.56 kDa
Ligands: QL8
Released: 5 Aug 2020

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

Secondary structure: helices and β-sheets

6ZHC contains 32 α-helices and 27 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 AAA: 7 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	71-78	8	1
α-helix	83	1
β-strand	84-89	6	2
β-strand	95-97	3	2
β-strand	101	1	2
β-strand	106-112	7	1
β-strand	116-121	6	2
β-strand	127	1	2
β-strand	129-130	2	1
β-strand	133	1	1
β-strand	136	1	2
α-helix	140-141	2
α-helix	145-146	2
β-strand	147-152	6	1
α-helix	158-169	12
α-helix	172-177	6
α-helix	182-189	8
α-helix	194-208	15

Chain BBB: 9 helices, 13 β-strands

Element	Residues	Length	Sheet
β-strand	2-9	8	3
β-strand	10	1	4
β-strand	12-19	8	3
β-strand	23	1	5
α-helix	24-35	12
α-helix	39-41	3
β-strand	42-46	5	3
β-strand	49-50	2	3
α-helix	51-52	2
β-strand	56	1	5
α-helix	57-60	4
β-strand	68	1	6
β-strand	71	1	6
α-helix	72	1
β-strand	73-79	7	3
β-strand	80	1	7
β-strand	85	1	7
α-helix	86-88	3
β-strand	90	1	4
α-helix	91-94	4
α-helix	96-100	5
α-helix	101-103	3

Chain CCC: 4 helices, 3 β-strands

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

Chain DDD: 12 helices, 0 β-strands

Element	Residues	Length
α-helix	1-20	20
α-helix	25-27	3
α-helix	83-96	14
α-helix	97-101	5
α-helix	102-104	3
α-helix	108-110	3
α-helix	120-130	11
α-helix	137-156	20
α-helix	162-173	12
α-helix	174-178	5
α-helix	179-184	6
α-helix	187-195	9

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
von Hippel-Lindau disease tumor suppressor	AAA	protein	155	Homo sapiens	P40337 (AlphaFold model)
Elongin-B	BBB	protein	107	Homo sapiens	Q15370 (AlphaFold model)
Elongin-C	CCC	protein	96	Homo sapiens	Q15369 (AlphaFold model)
Bcl-2-like protein 1	DDD	protein	221	Homo sapiens	Q07817 (AlphaFold model)

Sequence of entity 1 (AAA), FASTA

>6ZHC_1 von Hippel-Lindau disease tumor suppressor (chains AAA)
PRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWL
FRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRL
DIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD

Sequence of entity 2 (BBB), FASTA

>6ZHC_2 Elongin-B (chains BBB)
MDVFLMIRRHKTTIFTDAKESSTVFELKRIVEGILKRPPDEQRLYKDDQLLDDGKTLGEC
GFTSQTARPQAPATVGLAFRADDTFEALCIEPFSSPPELPDVMKPQD

Sequence of entity 3 (CCC), FASTA

>6ZHC_3 Elongin-C (chains CCC)
MYVKLISSDGHEFIVKREHALTSGTIKAMLSGPGQFAENETNEVNFREIPSHVLSKVCMY
FTYKVRYTNSSTEIPEFPIAPEIALELLMAANFLDC

Sequence of entity 4 (DDD), FASTA

>6ZHC_4 Bcl-2-like protein 1 (chains DDD)
MSMAMSQSNRELVVDFLSYKLSQKGYSWSQFSDVEENRTEAPEGTESEMETPSAINGNPS
WHLADSPAVNGATGHSSSLDAREVIPMAAVKQALREAGDEFELRYRRAFSDLTSQLHITP
GTAYQSFEQVVNELFRDGVNWGRIVAFFSFGGALCVESVDKEMQVLVSRIAAWMATYLND
HLEPWIQENGGWDTFVELYGNNAAAESRKGQERLEHHHHHH

Ligands and cofactors

ID	Name	Formula	Copies
QL8	2-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1~{H}-isoquinolin-2-yl]-5-[3-…	C68 H80 N8 O14 S3	1

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

Primary citation

Structural Insights into PROTAC-Mediated Degradation of Bcl-xL. Chung, C.W., Dai, H., Fernandez, E. et al. ACS Chem Biol (2020) 15:2316-2323. DOI 10.1021/acschembio.0c00266 · PubMed

Other PDB entries of the same protein (UniProt P40337 (AlphaFold model), which also has an AlphaFold model), best resolution first:

7Z76 1.32 Å, Crystal structure of compound 10 in complex with the bromodomain of human SMARCA2 and…
9GIO 1.49 Å, Crystal structure of the VHL-EloC-EloB complex with a covalent compound bound to C77 of…
7JTO 1.7 Å, Crystal structure of Protac MS33 in complex with the WD repeat-containing protein 5 and…
8BDS 1.72 Å, Ternary complex between VCB, BRD4-BD1 and PROTAC 48
4AJY 1.73 Å, von Hippel-Lindau protein-ElonginB-ElonginC complex, bound to Hif1- alpha peptide
6GMR 1.75 Å, pVHL:EloB:EloC in complex with (4-(1H-pyrrol-1-yl)phenyl)methanol
6HR2 1.76 Å, Crystal structure of PROTAC 2 in complex with the bromodomain of human SMARCA4 and…
6I7Q 1.8 Å, Structure of pVHL-elongin B-elongin C (VCB) in complex with hydroxylated-HIF-2alpha…
8BB3 1.8 Å, Structure of human WDR5 and pVHL:ElonginC:ElonginB bound to PROTAC with PEG linker…
6GFX 1.83 Å, pVHL:EloB:EloC in complex with modified HIF-1a CODD peptide containing…
1LM8 1.85 Å, Structure of a HIF-1a-pVHL-ElonginB-ElonginC Complex
6GMN 1.94 Å, pVHL:EloB:EloC in complex with methyl 4H-furo[3,2-b]pyrrole-5-carboxylate

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