Structure-activity relationship guides enantiomeric preference among potent inhibitors of B. anthracis dihydrofolate reductase

Structure

x-ray diffraction · 1 distinct chain · 23% helix, 33% strand (DSSP).

Ligands and binding sites

• 53I · (2E)-3-{5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl}-1-[(1R)-1-(2-methylprop-1-en-1-yl)phthalazin-2(1H)-y l]prop-2-en-1-one · ligand · 8 copies · chains A, H, C, B, G, F, D, E
• 53J · (2E)-3-{5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl}-1-[(1S)-1-(2-methylprop-1-en-1-yl)phthalazin-2(1H)-y l]prop-2-en-1-one · ligand · chains D
• CA · Calcium ion · metal · 8 copies · chains A, H, C, B, G, F, D, E
• CL · Chloride ion · ion · 8 copies · chains A, H, C, B, G, F, D, E

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

Pockets

13 pockets found on a 1 Å grid, 10 with a druggability of 0.5 or more.

Interfaces

15 interfaces between chains.

• B–F · 458 Ų buried · 5 hydrogen bonds · protein-protein
• H–B · 441 Ų buried · 5 hydrogen bonds · protein-protein
• A–C · 440 Ų buried · 4 hydrogen bonds · protein-protein
• G–F · 433 Ų buried · 5 hydrogen bonds · protein-protein
• D–E · 429 Ų buried · 4 hydrogen bonds · protein-protein

Compared structures

• 4ELH · Structure-activity relationship guides enantiomeric preference among potent inhibitors of… · the same entry in another collection · 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 Q81R22
• Elsewhere: RCSB PDB 4ELH · PDBe 4ELH · UniProt Q81R22