Structure of cysteine-free human insulin-degrading enzyme in complex with glucagon and substrate-selective macrocyclic inhibitor 63

Structure

x-ray diffraction · 2 distinct chains · 44% helix, 20% strand (DSSP).

Ligands and binding sites

• J22 · {(8R,9S,10S)-9-(2',3'-dimethyl[1,1'-biphenyl]-4-yl)-6-[(1-methyl-1H-imidazol-2-yl)sulfonyl]-1,6-diazabicyclo[6.2.0]decan-10-yl}methanol · ligand · 2 copies · chains A, C, B, D
• EPE · 4-(2-hydroxyethyl)-1-piperazine ethanesulfonic acid · additive · 2 copies · chains A, B
• PEG · Di(hydroxyethyl)ether · additive · 2 copies · chains A, B
• DIO · 1,4-diethylene dioxide · additive · 2 copies · chains A, B

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

Pockets

20 pockets found on a 1 Å grid, 11 with a druggability of 0.5 or more.

Interfaces

3 interfaces between chains.

• A–C · 1041 Ų buried · 23 hydrogen bonds · protein-protein
• B–D · 1017 Ų buried · 23 hydrogen bonds · protein-protein
• A–B · 880 Ų buried · 9 hydrogen bonds · protein-protein

Compared structures

• 6EDS · Structure of Cysteine-free Human Insulin-Degrading Enzyme in complex with Glucagon and… · the same entry in another collection · chain B against B, TM-score 1.00
• P01275 · AlphaFold monomer V2.0 prediction for pro-glucagon (P01275) · a predicted model of the same protein · chain C against A, TM-score 0.29

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 P14735
• Every structure of UniProt P01275
• Elsewhere: RCSB PDB 6EDS · PDBe 6EDS · UniProt P14735 · UniProt P01275