Multiple Conformers in Active Site of Human Dihydrofolate Reductase F31R/Q35E Double Mutant Suggest Structural Basis for Methotrexate Resistance

Methotrexate is a slow, tight-binding, competitive inhibitor of human dihydrofolate reductase (hDHFR), an enzyme that provides key metabolites for nucleotide biosynthesis. In an effort to better characterize ligand binding in drug resistance, we have previously engineered hDHFR variant F31R/Q35E. Th...

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Detalhes bibliográficos
Main Authors: Volpato, Jordan P., Yachnin, Brahm J., Blanchet, Jonathan, Guerrero, Vanessa, Poulin, Lucie, Fossati, Elena, Berghuis, Albert M., Pelletier, Joelle N.
Formato: Artigo
Idioma:Inglês
Publicado em: American Society for Biochemistry and Molecular Biology 2009
Assuntos:
Enzyme Catalysis and Regulation
Acesso em linha:https://ncbi.nlm.nih.gov/pmc/articles/PMC2740434/
https://ncbi.nlm.nih.gov/pubmed/19478082
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1074/jbc.M109.018010
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