Modulation of the ribonucleotide reductase M1-gemcitabine interaction in vivo by N-ethylmaleimide

► Gemcitabine induces a RRM1 conformational change in tumor cell lines and xenografts. ► The 110 kDa RRM1 is unique to gemcitabine interaction among 12 cytotoxic agents. ► The 110 kDa RRM1 can be stabilized by the thiol alkylator N-ethylmaleimide. ► C218A, C429A, and E431A mutations in RRM1 abolished the conformational change. ► The 110 kDa RRM1 may be a specific biomarker of gemcitabine's therapeutic efficacy.