Dihydrofolate reductase: x-ray structure of the binary complex with methotrexate.
A central eight-stranded beta-pleated sheet is the main feature of the polypeptide backbone folding in dihydrofolate reductase. The innermost four strands and two bridging helices are geometrically similar to but are connected in a different way from those in the dinucleotide binding domains found in nicotinamide-adenine dinucleotide-linked dehydrogenases. Methotrexate is bound in a 15-angstrom-deep cavity with the pteridine ring buried in a primarily hydrophobic pocket, although a strong interaction occurs between the side chain of aspartic acid 27 and N(1), N(8), and the 2-amino group of methotrexate.
D001665:Binding Sites; D004926:Escherichia coli / Q000201:enzymology; D005493:Folic Acid Antagonists; D008727:Methotrexate / Q000378:metabolism / Q000494:pharmacology; D008968:Molecular Conformation; D009249:NADP / Q000378:metabolism; D011487:Protein Conformation; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism; D014961:X-Ray Diffraction
D005493:Folic Acid Antagonists; D009249:NADP; D013762:Tetrahydrofolate Dehydrogenase; D008727:Methotrexate