7Z76: Compound 10

Crystal structure of compound 10 in complex with the bromodomain of human SMARCA2 and pVHL:ElonginC:ElonginB. Determined by X-ray diffraction at 1.32 Å resolution. Released 14 Sept 2022.

Method: X-ray diffraction
Resolution: 1.32 Å
Organism: Homo sapiens
Chains: 4
Atoms: 4,396
Mol. weight: 57.77 kDa
Ligands: IFJ
Released: 14 Sept 2022

Explore 7Z76 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7Z76 contains 30 α-helices and 29 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 A: 9 helices, 13 β-strands

Element	Residues	Length	Sheet
β-strand	2-9	8	1
β-strand	10	1	2
β-strand	12-19	8	1
β-strand	23	1	3
α-helix	24-35	12
α-helix	39-41	3
β-strand	42-46	5	1
β-strand	49-50	2	1
α-helix	51-52	2
β-strand	56	1	3
α-helix	57-60	4
α-helix	64-66	3
β-strand	68	1	4
β-strand	71	1	4
α-helix	72	1
β-strand	73-79	7	1
β-strand	80-81	2	5
β-strand	84-85	2	5
α-helix	86-88	3
β-strand	90	1	2
α-helix	91-100	10
α-helix	101-103	3

Chain B: 6 helices, 3 β-strands

Element	Residues	Length	Sheet
β-strand	18-22	5	1
β-strand	28-32	5	1
α-helix	33-36	4
α-helix	40-46	7
β-strand	59-61	3	1
α-helix	67-83	17
α-helix	89-92	4
α-helix	97-99	3
α-helix	100-110	11

Chain C: 6 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	71-78	8	6
α-helix	83	1
β-strand	84-89	6	7
β-strand	95-97	3	7
β-strand	101	1	7
β-strand	106-112	7	6
β-strand	116-121	6	7
β-strand	127	1	7
β-strand	129-130	2	6
β-strand	133	1	6
β-strand	136	1	7
α-helix	145-146	2
β-strand	147-152	6	6
α-helix	158-169	12
α-helix	172-177	6
α-helix	183-189	7
α-helix	194-201	8

Chain D: 9 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	1378-1380	3
α-helix	1381-1396	16
β-strand	1398	1	8
β-strand	1404	1	8
α-helix	1407-1409	3
α-helix	1412-1414	3
α-helix	1419-1424	6
α-helix	1431-1439	9
α-helix	1446-1463	18
α-helix	1465	1
α-helix	1469-1486	18

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Elongin-B	A	protein	104	Homo sapiens	Q15370 (AlphaFold model)
Elongin-C	B	protein	97	Homo sapiens	Q15369 (AlphaFold model)
von Hippel-Lindau disease tumor suppressor	C	protein	162	Homo sapiens	P40337 (AlphaFold model)
Probable global transcription activator SNF2L2	D	protein	123	Homo sapiens	P51531 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>7Z76_1 Elongin-B (chains A)
MDVFLMIRRHKTTIFTDAKESSTVFELKRIVEGILKRPPDEQRLYKDDQLLDDGKTLGEC
GFTSQTARPQAPATVGLAFRADDTFEALCIEPFSSPPELPDVMK

Sequence of entity 2 (B), FASTA

>7Z76_2 Elongin-C (chains B)
MMYVKLISSDGHEFIVKREHALTSGTIKAMLSGPGQFAENETNEVNFREIPSHVLSKVCM
YFTYKVRYTNSSTEIPEFPIAPEIALELLMAANFLDC

Sequence of entity 3 (C), FASTA

>7Z76_3 von Hippel-Lindau disease tumor suppressor (chains C)
GSMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHS
YRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVK
PENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD

Sequence of entity 4 (D), FASTA

>7Z76_4 Probable global transcription activator SNF2L2 (chains D)
SMAEKLSPNPPKLTKQMNAIIDTVINYKDSSGRQLSEVFIQLPSRKELPEYYELIRKPVD
FKKIKERIRNHKYRSLGDLEKDVMLLCHNAQTFNLEGSQIYEDSIVLQSVFKSARQKIAK
EEE

Ligands and cofactors

ID	Name	Formula	Copies
IFJ	(2~{S},4~{R})-~{N}-[(1~{R})-2-[(2~{R})-1-[4-(4-bromanyl-7-cyclopentyl-5-oxidany…	C56 H70 Br N9 O6 S	1

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

Primary citation

A selective and orally bioavailable VHL-recruiting PROTAC achieves SMARCA2 degradation in vivo. Kofink, C., Trainor, N., Mair, B. et al. Nat Commun (2022) 13:5969-5969. DOI 10.1038/s41467-022-33430-6 · PubMed

Other PDB entries of the same protein (UniProt Q15370 (AlphaFold model), which also has an AlphaFold model), best resolution first:

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…
7ZLM 1.79 Å, Crystal structure of SOCS2:ElonginB:ElonginC in complex with compound MN551
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
9D1Z 1.88 Å, Structure of G75Q Ubiquitin bound to KLHDC3-EloB/C

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