Human dihydrofolate reductase complexed with NADPH and a lipophilic antifolate selective for mycobacterium avium DHFR, 6-((2,5- DIETHOXYPHENYL)AMINOMETHYL)-2,4-diamino-5-METHYLPYRIDO(2,3-D) pyrimidine (sri-8686)

Structure

x-ray diffraction · 2 distinct chains · 19% helix, 33% strand (DSSP).

Ligands and binding sites

• NDP · Nadph dihydro-nicotinamide-adenine-dinucleotide phosphate · ligand · 2 copies · chains A, B
• VG9 · 6-{[(2,5-diethoxyphenyl)amino]methyl}-5-methylpyrido[2,3-d]pyrimidine-2,4-diamine · ligand · 2 copies · chains A, B
• FOL · Folic acid · ligand · 2 copies · chains A, B
• K · Potassium ion · metal · 2 copies · chains A, B

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

Pockets

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

Interfaces

1 interface between chains.

• A–B · 273 Ų buried · 2 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 1 covalent (covalent ligand).

Compared structures

• 2W3B · Human dihydrofolate reductase complexed with NADPH and a lipophilic antifolate selective… · the same entry in another collection · chain A against A, TM-score 1.00
• P00374 · AlphaFold monomer V2.0 prediction for dihydrofolate reductase (P00374) · a predicted model of the same protein · chain A against A, TM-score 0.98

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 P00374
• Elsewhere: RCSB PDB 2W3B · PDBe 2W3B · UniProt P00374