Structure-based evolution of a hybrid steroid series of autotaxin inhibitors

Structure

x-ray diffraction · 1 distinct chain · 30% helix, 19% strand (DSSP).

Ligands and binding sites

• 7CF · [3,5-bis(chloranyl)phenyl]methyl (3~{R})-3-[[(4~{R})-4-[(3~{R},5~{S},7~{S},8~{R},9~{S},10~{S},13~{R},14~{S}, 17~{R})-10,13-dimethyl-3,7-bis(oxidanyl)-2,3,4,5,6,7, 8,9,11,12,14,15,16,17-tetradecahydro-1~{H}-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]pyrrolidine-1-carboxylate · ligand · chains A
• NKP · (2R)-2-hydroxy-3-(phosphonooxy)propyl (9E)-octadec-9-enoate · ligand · chains A
• MAN · alpha-D-mannopyranose · sugar · 6 copies · chains A
• NAG · 2-acetamido-2-deoxy-beta-D-glucopyranose · sugar · 2 copies · chains A
• BMA · beta-D-mannopyranose · sugar
• ZN · Zinc ion · metal · 2 copies · chains A
• NA · Sodium ion · metal · 2 copies · chains A
• CA · Calcium ion · metal · chains A
• IOD · Iodide ion · ion · 12 copies · chains A
• SCN · Thiocyanate ion · ion · 10 copies · chains A
• GOL · Glycerol · additive · 7 copies · chains A

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

Pockets

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

Modifications

Observed in the structure: 14 disulfide, 1 glycan (disulfide, N-glycosylation).

Compared structures

• 5M0M · Structure-based evolution of a hybrid steroid series of Autotaxin inhibitors · the same entry in another collection · chain A against A, TM-score 1.00
• Q64610 · AlphaFold monomer V2.0 prediction for ectonucleotide PYROPHOSPHATASE/PHOSPHODIESTERASE… · a predicted model of the same protein · chain A 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 Q64610
• Elsewhere: RCSB PDB 5M0M · PDBe 5M0M · UniProt Q64610