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PubMed · 17920

Dihydrofolate reductase: x-ray structure of the binary complex with methotrexate.

D A Matthews·R A Alden·J T Bolin·S T Freer·R Hamlin·N Xuong·J Kraut·M Poe·M Williams·K Hoogsteen
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Abstract

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.

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Binding SitesEscherichia coliFolic Acid AntagonistsMethotrexateMolecular ConformationNADPProtein ConformationTetrahydrofolate DehydrogenaseX-Ray DiffractionJournal ArticleResearch Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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D A Matthews, R A Alden, J T Bolin, S T Freer, R Hamlin, N Xuong, J Kraut, M Poe, M Williams, K Hoogsteen. 1977-07-29. Dihydrofolate reductase: x-ray structure of the binary complex with methotrexate.. https://doi.org/10.1126/science.17920

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