Crystal structure of recombinant human beta-glucocerebrosidase in complex with biphenyl-cyclophellitol inhibitor (ME655)

Structure

x-ray diffraction · 2 distinct chains · 28% helix, 28% strand (DSSP).

Ligands and binding sites

• HK2 · (1~{S},3~{S},4~{R},6~{R})-2,3,4,6-tetrakis(oxidanyl)-5-[[4-[3-(4-phenylphenoxy)propyl]-1,2,3-triazol-1-yl]methyl]cyclohexan-1-olate · ligand · 2 copies · chains A, B
• NAG · 2-acetamido-2-deoxy-beta-D-glucopyranose · sugar · 5 copies · chains A, B
• SO4 · Sulfate ion · ion · 15 copies · chains A, B
• ACT · Acetate ion · additive · 24 copies · chains A, B

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

Pockets

8 pockets found on a 1 Å grid, 3 with a druggability of 0.5 or more.

Interfaces

1 interface between chains.

• A–B · 461 Ų buried · 3 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 4 disulfide, 3 glycan, 2 covalent (disulfide, N-glycosylation, covalent ligand).

Compared structures

• 6Q6N · Crystal structure of recombinant human beta-glucocerebrosidase in complex with… · the same entry in another collection · chain A against A, TM-score 1.00
• P04062 · AlphaFold monomer V2.0 prediction for lysosomal acid glucosylceramidase (P04062) · a predicted model of the same protein · chain B against A, TM-score 1.00

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 P04062
• Elsewhere: RCSB PDB 6Q6N · PDBe 6Q6N · UniProt P04062