Article
Structural insights into the hydrolysis and polymorphism of methotrexate polyglutamate by zebrafish γ-glutamyl hydrolase.
Journal of medicinal chemistry - 10 Oct 2013
Chuankhayan Phimonphan, Kao Tseng-Ting, Lin Chien-Chih, Guan Hong-Hsiang, Nakagawa Atsushi, Fu Tzu-Fun, Chen Chun-Jung
Abstract excerpt
γ-Glutamyl hydrolases (γGH) catalyze the hydrolysis of γ-linked glutamate residues from the polyglutamyl of folates and antifolates, such as methotrexate (MTX), a widely used anticancer drug. We describe the first crystal structures of the endopeptidase-type γGH (zγGH) from zebrafish and the mutant complexes with MTX(Glu)5 and hydrolyzed MTX(Glu)1, revealing the complete set of key residues involved in hydrolysis...
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