Crystal structure of human neutrophil elastase in complex with a dihydropyrimidone inhibitor

Structure

x-ray diffraction · 1 distinct chain · 9% helix, 39% strand (DSSP).

Ligands and binding sites

• JJV · (6S)-6-(4-cyano-2-methylsulfonyl-phenyl)-4-methyl-2-oxidanylidene-3-[3-(trifluoromethyl)phenyl]-1,6-dihydropyrimidine-5-carbonitrile · ligand · 2 copies · chains A, B
• NAG · 2-acetamido-2-deoxy-beta-D-glucopyranose · sugar · 6 copies · chains A, B
• FUC · alpha-L-fucopyranose · sugar · 4 copies · chains A, B
• MES · 2-(N-morpholino)-ethanesulfonic acid · additive · 2 copies · chains A, B
• XPE · 3,6,9,12,15,18,21,24,27-nonaoxanonacosane-1,29-diol · additive · chains A, B

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

Pockets

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

Interfaces

1 interface between chains.

• A–B · 797 Ų buried · 6 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 8 disulfide, 4 glycan (disulfide, N-glycosylation).

Compared structures

• 5A0C · Crystal Structure of human neutrophil elastase in complex with a dihydropyrimidone… · the same entry in another collection · chain A against A, TM-score 1.00
• P08246 · AlphaFold monomer V2.0 prediction for neutrophil elastase (P08246) · 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 P08246
• Elsewhere: RCSB PDB 5A0C · PDBe 5A0C · UniProt P08246