Dihydrofolate reductase from Lactobacillus casei. X-ray structure of the enzyme methotrexate.NADPH complex.
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Amino Acid Sequence↗
Biomedical subjects
R Hamlin
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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.
Binding Sites↗