Structure of itraconazole-bound NPC1

Structure

electron microscopy · 1 distinct chain · 44% helix, 9% strand (DSSP).

Ligands and binding sites

• QDG · 4-(3-bromo-4-{4-[4-({(2R,4S)-2-(2,4-dichlorophenyl)-2-[(1H-1,2,4-triazol-1-yl)methyl]-1,3-dioxolan-4-yl}methoxy)phenyl]piperazin-1-yl}phenyl)-2-[(2S)-butan-2-yl]-2,4-dihydro-3H-1,2,4-triazol-3-one · ligand · chains A
• NAG · 2-acetamido-2-deoxy-beta-D-glucopyranose · sugar · 12 copies · chains A
• MAN · alpha-D-mannopyranose · sugar · chains A

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

Pockets

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

Modifications

Observed in the structure: 15 disulfide, 10 glycan (disulfide, N-glycosylation).

Compared structures

• 6UOX · Structure of itraconazole-bound NPC1 · the same entry in another collection · chain A against A, TM-score 1.00
• O15118 · AlphaFold monomer V2.0 prediction for npc intracellular cholesterol transporter 1 (O15118) · a predicted model of the same protein · chain A against A, TM-score 0.88

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 O15118
• Elsewhere: RCSB PDB 6UOX · PDBe 6UOX · UniProt O15118