MolNFT v1 · #97270 · protein

Hydroxyethylamine-based inhibitors of BACE1: P1-P3 macrocyclization can improve potency, selectivity, and cell activity

4K8S · Beta-secretase 1: “Hydroxyethylamine-based inhibitors of BACE1: P1-P3 macrocyclization can improve potency, selectivity, and…”. X-ray diffraction, 1 ligand (1QT), 8 pockets (best druggability 0.71). MolNFT v1 #97270 on GenesisL1: 3D…

PDB: 4K8S
Type: protein
Length: 1,113 residues
Chains: 3
Method: x-ray diffraction
Collection: MolNFT v1 / PDB
Contract: 0xDE3723766Bc32dcACD03C17BaA400A7B36837Eba
Owner: 0x3396CDB397284571d12822B4ae1189a8E22AAAAA
Molecule: Beta-secretase 1
EC: 3.4.23.46
UniProt: P56817
Ligands: 1QT
Pockets: 8 · best druggability 0.71

Structure

x-ray diffraction · 2 distinct chains · 15% helix, 42% strand (DSSP).

Chain	Molecule	Type	Residues	Secondary structure	UniProt
A	Beta-secretase 1 (EC 3.4.23.46)	protein	371	15% helix, 42% strand	P56817
B, C	Beta-secretase 1 (EC 3.4.23.46)	protein	371	16% helix, 42% strand	P56817

Ligands and binding sites

1QT · (3S)-3-[(1R)-2-{[(4S)-6-ethyl-3,4-dihydrospiro[chromene-2,1'-cyclobutan]-4-yl]amino}-1-hydroxyethyl]-4-azabicyclo[11.3.1]heptadeca-1(17),13,15-trien-5-one · ligand · 3 copies · chains A, B, C

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

Pockets

8 pockets found on a 1 Å grid, 7 with a druggability of 0.5 or more.

Pocket	Volume (Å³)	Druggability	Buriedness	Lining residues	Inside
1	443	0.71	0.81	56	1QT
2	466	0.71	0.81	65	1QT
3	512	0.70	0.80	58	1QT
4	419	0.66	0.79	60	empty
5	157	0.56	0.82	30	empty

Interfaces

3 interfaces between chains.

B–C · 1131 Å² buried · 10 hydrogen bonds · protein-protein
A–B · 474 Å² buried · 1 hydrogen bond · protein-protein
A–C · 425 Å² buried · 2 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 9 disulfide (disulfide).

Compared structures

4K8S · Hydroxyethylamine-based inhibitors of BACE1: P1-P3 macrocyclization can improve potency… · the same entry in another collection · chain A against A, TM-score 1.00
P56817 · AlphaFold monomer V2.0 prediction for beta-secretase 1 (P56817) · a predicted model of the same protein · chain A against A, TM-score 0.99

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 P56817
Elsewhere: RCSB PDB 4K8S · PDBe 4K8S · UniProt P56817

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