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

Structure

x-ray diffraction · 1 distinct chain · 22% helix, 34% strand (DSSP).

Ligands and binding sites

• 34S · (2E)-3-{5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl}-1-[(1S)-1-phenylphthalazin-2(1H)-yl]prop-2-en-1-one · ligand · 6 copies · chains A, H, B, G, F, E
• 34R · (2E)-3-{5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl}-1-[(1R)-1-phenylphthalazin-2(1H)-yl]prop-2-en-1-one · ligand · 4 copies · chains C, F, D, E
• 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

11 pockets found on a 1 Å grid, 9 with a druggability of 0.5 or more.

Interfaces

16 interfaces between chains.

• B–F · 447 Ų buried · 5 hydrogen bonds · protein-protein
• H–B · 446 Ų buried · 6 hydrogen bonds · protein-protein
• G–F · 418 Ų buried · 5 hydrogen bonds · protein-protein
• D–E · 418 Ų buried · 5 hydrogen bonds · protein-protein
• A–C · 415 Ų buried · 4 hydrogen bonds · protein-protein

Compared structures

• 4ELB · Structure-activity relationship guides enantiomeric preference among potent inhibitors of… · the same entry in another collection · chain C against C, 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 4ELB · PDBe 4ELB · UniProt Q81R22