7Z6L: PROTAC 5

Crystal structure of PROTAC 5 in complex with the bromodomain of human SMARCA2 and pVHL:ElonginC:ElonginB. Determined by X-ray diffraction at 2.24 Å resolution. Released 7 Sept 2022.

Method: X-ray diffraction
Resolution: 2.24 Å
Organism: Homo sapiens
Chains: 4
Atoms: 3,734
Mol. weight: 56.84 kDa
Ligands: IEI
Released: 7 Sept 2022

Explore 7Z6L in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7Z6L contains 29 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: 8 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	1-15	15
β-strand	18	1	1
β-strand	24	1	1
α-helix	27-29	3
α-helix	32-34	3
α-helix	39-44	6
α-helix	51-59	9
α-helix	66-83	18
α-helix	85	1
α-helix	89-109	21

Chain B: 7 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	71-78	8	2
α-helix	83	1
β-strand	84-89	6	3
β-strand	95-97	3	3
β-strand	101	1	3
β-strand	106-112	7	2
β-strand	116-121	6	3
β-strand	127	1	3
β-strand	129-130	2	2
β-strand	133	1	2
β-strand	136	1	3
α-helix	142-144	3
α-helix	146	1
β-strand	147-152	6	2
α-helix	158-169	12
α-helix	172-177	6
α-helix	182-189	8
α-helix	194-208	15

Chain C: 6 helices, 3 β-strands

Element	Residues	Length	Sheet
β-strand	18-22	5	4
β-strand	28-32	5	4
α-helix	33-36	4
α-helix	40-45	6
β-strand	59-61	3	4
α-helix	67-83	17
α-helix	89-92	4
α-helix	97-99	3
α-helix	100-110	11

Chain D: 8 helices, 13 β-strands

Element	Residues	Length	Sheet
β-strand	2-9	8	4
β-strand	10	1	5
β-strand	12-19	8	4
β-strand	23	1	6
α-helix	24-35	12
α-helix	39-41	3
β-strand	42-46	5	4
β-strand	49-50	2	4
α-helix	51-52	2
β-strand	56	1	6
α-helix	57-60	4
β-strand	68	1	7
β-strand	71	1	7
α-helix	72	1
β-strand	73-79	7	4
β-strand	80-81	2	8
β-strand	84-85	2	8
α-helix	86-88	3
β-strand	90	1	5
α-helix	94-96	3
α-helix	98-100	3

Molecules and chains

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

Sequence of entity 1 (A), FASTA

>7Z6L_1 Probable global transcription activator SNF2L2 (chains A)
SMAEKLSPNPPKLTKQMNAIIDTVINYKDSSGRQLSEVFIQLPSRKELPEYYELIRKPVD
FKKIKERIRNHKYRSLGDLEKDVMLLCHNAQTFNLEGSQIYEDSIVLQSVFKSARQKIAK
EEE

Sequence of entity 2 (B), FASTA

>7Z6L_2 von Hippel-Lindau disease tumor suppressor (chains B)
GSMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHS
YRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVK
PENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD

Sequence of entity 3 (C), FASTA

>7Z6L_3 Elongin-C (chains C)
MMYVKLISSDGHEFIVKREHALTSGTIKAMLSGPGQFAENETNEVNFREIPSHVLSKVCM
YFTYKVRYTNSSTEIPEFPIAPEIALELLMAANFLDC

Sequence of entity 4 (D), FASTA

>7Z6L_4 Elongin-B (chains D)
MDVFLMIRRHKTTIFTDAKESSTVFELKRIVEGILKRPPDEQRLYKDDQLLDDGKTLGEC
GFTSQTARPQAPATVGLAFRADDTFEALCIEPFSSPPELPDVMK

Ligands and cofactors

ID	Name	Formula	Copies
IEI	(2~{S},4~{R})-~{N}-[[2-[3-[4-(4-bromanyl-7-cyclopentyl-5-oxidanylidene-benzimid…	C53 H62 Br F N8 O6 S	1

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 P51531 (AlphaFold model), which also has an AlphaFold model), best resolution first:

6HAZ 1.31 Å, Crystal structure of the bromodomain of human SMARCA2 in complex with SMARCA-BD ligand
7Z76 1.32 Å, Crystal structure of compound 10 in complex with the bromodomain of human SMARCA2 and…
7Z78 1.32 Å, Crystal structure of compound 4 in complex with the bromodomain of human SMARCA2 and…
5DKC 1.6 Å, Crystal structure of the bromodomain of human BRM (SMARCA2) in complex with PFI-3…
9D11 1.68 Å, Smarca2 Bromodomain in complex with compound 22
5DKH 1.7 Å, Crystal structure of the bromodomain of human BRM (SMARCA2) in complex with a…
9E30 1.71 Å, Discovery of Potent, Highly Selective and Efficacious SMARCA2 Degraders - Compound 13
9E31 1.96 Å, Discovery of Potent, Highly Selective and Efficacious SMARCA2 Degraders - Compound 6
4QY4 1.97 Å, Crystal structure of the bromodomain of human SMARCA2
7Z77 1.97 Å, Crystal structure of compound 6 in complex with the bromodomain of human SMARCA2 and…
9QAC 2.07 Å, Crystal structure of the SMARCA2 bromodomain bound to a fragment screening hit
9QAD 2.08 Å, Crystal structure of the SMARCA2 bromodomain bound to a tricyclic pyrimidoindolone…

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