6HR2: PROTAC 2

Crystal structure of PROTAC 2 in complex with the bromodomain of human SMARCA4 and pVHL:ElonginC:ElonginB. Determined by X-ray diffraction at 1.76 Å resolution. Released 12 Jun 2019.

Method: X-ray diffraction
Resolution: 1.76 Å
Organism: Homo sapiens
Chains: 8
Atoms: 8,048
Mol. weight: 110.47 kDa
Ligands: FWZ
Released: 12 Jun 2019

Explore 6HR2 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

6HR2 contains 52 α-helices and 58 β-strands across 8 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	1453-1455	3
α-helix	1456-1471	16
β-strand	1473	1	1
β-strand	1480	1	1
α-helix	1483-1485	3
α-helix	1488-1490	3
α-helix	1495-1500	6
α-helix	1507-1515	9
α-helix	1522-1540	19
α-helix	1545-1567	23

Chain B: 8 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	140-141	2
α-helix	142-144	3
α-helix	145-146	2
β-strand	147-152	6	2
α-helix	158-169	12
α-helix	172-174	3
α-helix	183-189	7
α-helix	194-208	15

Chain C: 4 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	40-46	7
β-strand	59-61	3	4
α-helix	67-83	17
α-helix	100-110	11

Chains D and H: 7 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
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	91-93	3
α-helix	98-100	3

Chain E: 8 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	1452-1455	4
α-helix	1456-1471	16
β-strand	1473	1	9
β-strand	1480	1	9
α-helix	1483-1485	3
α-helix	1488-1490	3
α-helix	1495-1500	6
α-helix	1507-1515	9
α-helix	1522-1540	19
α-helix	1545-1567	23

Chain F: 6 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	71-78	8	2
α-helix	83	1
β-strand	84-89	6	10
β-strand	95-97	3	10
β-strand	101	1	10
β-strand	106-112	7	2
β-strand	116-121	6	10
β-strand	127	1	10
β-strand	129-130	2	2
β-strand	133	1	2
β-strand	136	1	10
α-helix	145-146	2
β-strand	147-152	6	2
α-helix	158-169	12
α-helix	172-174	3
α-helix	182-189	8
α-helix	194-208	15

Chain G: 4 helices, 3 β-strands

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

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Transcription activator BRG1	A, E	protein	120	Homo sapiens	P51532 (AlphaFold model)
von Hippel-Lindau disease tumor suppressor	B, F	protein	149	Homo sapiens	P40337 (AlphaFold model)
Elongin-C	C, G	protein	97	Homo sapiens	Q15369 (AlphaFold model)
Elongin-B	D, H	protein	104	Homo sapiens	Q15370 (AlphaFold model)

Sequence of entity 1 (A, E), FASTA

>6HR2_1 Transcription activator BRG1 (chains A, E)
EKLSPNPPNLTKKMKKIVDAVIKYKDSSSGRQLSEVFIQLPSRKELPEYYELIRKPVDFK
KIKERIRNHKYRSLNDLEKDVMLLCQNAQTFNLEGSLIYEDSIVLQSVFTSVRQKIEKED

Sequence of entity 2 (B, F), FASTA

>6HR2_2 von Hippel-Lindau disease tumor suppressor (chains B, F)
PVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFR
DAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDI
VRSLYEDLEDHPNVQKDLERLTQERIAHQ

Sequence of entity 3 (C, G), FASTA

>6HR2_3 Elongin-C (chains C, G)
MMYVKLISSDGHEFIVKREHALTSGTIKAMLSGPGQFAENETNEVNFREIPSHVLSKVCM
YFTYKVRYTNSSTEIPEFPIAPEIALELLMAANFLDC

Sequence of entity 4 (D, H), FASTA

>6HR2_4 Elongin-B (chains D, H)
MDVFLMIRRHKTTIFTDAKESSTVFELKRIVEGILKRPPDEQRLYKDDQLLDDGKTLGEC
GFTSQTARPQAPATVGLAFRADDTFEALCIEPFSSPPELPDVMK

Ligands and cofactors

ID	Name	Formula	Copies
FWZ	(2~{S},4~{R})-~{N}-[[2-[2-[4-[[4-[3-azanyl-6-(2-hydroxyphenyl)pyridazin-4-yl]pi…	C49 H58 F N9 O6 S	2

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

Primary citation

BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design. Farnaby, W., Koegl, M., Roy, M.J. et al. Nat Chem Biol (2019) 15:672-680. DOI 10.1038/s41589-019-0294-6 · PubMed

Other PDB entries of the same protein (UniProt P51532 (AlphaFold model), which also has an AlphaFold model), best resolution first:

7TAB 1.16 Å, G-925 bound to the SMARCA4 (BRG1) Bromodomain
2GRC 1.5 Å, 1.5 A structure of bromodomain from human BRG1 protein, a central ATPase of SWI/SNF…
6ZS2 1.57 Å, Crystal Structure of the bromodomain of human transcription activator BRG1 (SMARCA4) in…
7TD9 1.61 Å, G-059 bound to the SMARCA4 (BRG1) Bromodomain
3UVD 1.85 Å, Crystal Structure of the bromodomain of human Transcription activator BRG1 (SMARCA4) in…
5DKD 2.0 Å, Crystal structure of the bromodomain of human BRG1 (SMARCA4) in complex with PFI-3…
5EA1 2.0 Å, Crystal Structure of SMARCA4 bromodomain in complex with MPD
9DTX 2.11 Å, Crystal structure of PRT3789 in complex with the bromodomain of human BRG1 (SMARCA4) and…
7VRB 2.39 Å, Structure of the Human BRG1/SS18 complex
9UXC 2.74 Å, The ADP-bound structure of BCL7B-containing ARP module of the human SWI/SNF complex
7VDT 2.8 Å, The motor-nucleosome module of human chromatin remodeling PBAF-nucleosome complex
9WBZ 2.9 Å, The structure of NCP-motor-ARP module of ncBAF-nucleosome complex

Browse structure collections

About this viewer

MolViewer shows 6HR2 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.