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Crystal structure of macrocyclic protac 1 in complex with the second bromodomain of human BRD4 and PVHL:ELONGINC:ELONGINB

Analyse Crystal structure of macrocyclic protac 1 in complex with the second… in the GL1X research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides, crosslinks and neighbours on the 3D structure.

PDB: 6SIS
Type: protein
Length: 902 residues
Chains: 8
Method: x-ray diffraction
Collection: MolNFT v1 / PDB
Contract: 0xDE3723766Bc32dcACD03C17BaA400A7B36837Eba
Owner: 0x3396CDB397284571d12822B4ae1189a8E22AAAAA
Molecule: Bromodomain-containing protein 4; Elongin-B; Elongin-C; Von hippel-lindau disease tumor…
UniProt: O60885, Q15370, Q15369, P40337
Ligands: LFE
Pockets: 10 · best druggability 0.70

Structure

x-ray diffraction · 4 distinct chains · 39% helix, 20% strand (DSSP).

Chain	Molecule	Type	Residues	Secondary structure	UniProt
A, E	Bromodomain-containing protein 4	protein	111	68% helix, 0% strand	O60885
B, F	Elongin-B	protein	104	18% helix, 35% strand	Q15370
C, G	Elongin-C	protein	87	48% helix, 14% strand	Q15369
D, H	Von hippel-lindau disease tumor suppressor	protein	149	28% helix, 27% strand	P40337

Ligands and binding sites

LFE · ~{N}-[(5~{S},7~{R},11~{S},23~{S})-11-~{tert}-butyl-34-(4-methyl-1,3-thiazol-5-yl)-7-oxidanyl-4,10,13-tris(oxidanylidene)-15,18,21,25,28,31-hexaoxa-3,9,12-triazatricyclo[30.4.0.0^{5,9}]hexatriaconta-1(32),33, 35-trien-23-yl]-2-[(7~{S},9~{S})-7-(4-chlorophenyl)-4, 5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.0^{2,6}]trideca-2(6),4,10,12-tetraen-9-yl]ethanamide · ligand · 2 copies · chains A, D, E, H

Binding sites are the residues within 4.5 Å of a ligand's heavy atoms.

Pockets

10 pockets found on a 1 Å grid, 2 with a druggability of 0.5 or more.

Pocket	Volume (Å³)	Druggability	Buriedness	Lining residues	Inside
1	608	0.70	0.78	53	LFE
2	615	0.70	0.78	66	LFE
3	157	0.50	0.78	26	empty
4	93	0.49	0.82	20	empty
5	154	0.48	0.77	27	empty

Interfaces

16 interfaces between chains.

B–C · 1161 Å² buried · 13 hydrogen bonds · protein-protein
F–G · 1141 Å² buried · 10 hydrogen bonds · protein-protein
G–H · 1088 Å² buried · 12 hydrogen bonds · protein-protein
C–D · 1086 Å² buried · 12 hydrogen bonds · protein-protein
D–H · 879 Å² buried · 11 hydrogen bonds · protein-protein

Compared structures

6SIS · Crystal structure of macrocyclic PROTAC 1 in complex with the second bromodomain of human… · the same entry in another collection · chain H against H, TM-score 1.00
Q15370 · AlphaFold monomer V2.0 prediction for elongin-B (Q15370) · a predicted model of the same protein · chain F against A, TM-score 0.99
Q15369 · AlphaFold monomer V2.0 prediction for elongin-C (Q15369) · a predicted model of the same protein · chain C against A, TM-score 0.98

Analyse

Open in the research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides and crosslinks on the 3D structure
Every structure of UniProt O60885
Every structure of UniProt Q15370
Every structure of UniProt Q15369
Every structure of UniProt P40337
Elsewhere: RCSB PDB 6SIS · PDBe 6SIS · UniProt O60885 · UniProt Q15370 · UniProt Q15369 · UniProt P40337

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