Work

Methotrexate binds in a non‐productive orientation to human dihydrofolate reductase in solution, based on NMR spectroscopy

Year: 1991

Type: article

Abstract: Dihydrofolate reductase (DHFR) is an intracellular target enzyme for folate antagonist drugs, including methotrexate. In order to compare the binding of methotrexate to human DHFR in solution with that observed in the crystalline state, NMR spectroscopy has been used to determine the conformation of the drug bound to human DHFR in solution. In agreement with what has been observed in the crystalline state, NOE's identified protein and methotrexate protons indicate that methotrexate binds in a non-productive orientation. In contrast to what has been reported for E. coli DHFR in solution, only one bound conformation of methotrexate is observed.

Source: FEBS Letters

DOI: 10.1016/0014-5793(91)80604-2

Authors: Brian J. Stockman, N.R. Nirmala, Gerhard Wagner, Tavner J. Delcamp, Michael T. DeYarman, James H. Freisheim

Institutions: Harvard University, University of Toledo Medical Center

Language: English

Topic: Protein Structure and Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Cancer Institute, National Institute of General Medical Sciences