Mutated constitutively activated forms of the BRAF kinase have been associated with various cancers, such as melanoma and leukemia. One such common BRAF mutant, BRAFV600E is found in about 50% of melanomas. BRAF is part of the MAPK signaling cascade that contains the downstream target MEK1/2, which phosphorylates ERK1/2 and subsequently increases cell proliferation. While the majority of the therapeutic inhibitors of the MAPK pathway have been designed to target BRAF, some have also targeted MEK1/2 as well as other kinases within the pathway such as ERK1/2. Recently, MEK1 has been observed to interact with copper (Cu). This element and copper transporter 1 (CTR1) were found to be important for kinase activity and when absent, decreased the ability of BRAFV600E to signal and mediate tumorigenesis. In this study, work was done to further characterize the MEK1-Cu interaction through crystallography, and carried out associated biochemical and enzymatic studies in order to characterize the functional consequence of the interaction and its effects on downstream ERK phosphorylation. A crystal structure of a MEK1-Cu complex was obtained revealing a Cu binding site to a regulatory site of the kinase that would be predicted to inhibit kinase activity. This structural observation is supported by functional studies with bacterially produced recombinant homogeneously purified MEK1 demonstrating that Cu inhibits MEK1 kinase activity in vitro. Interestingly, crudely purified MEK1 did show Cu-mediated MEK1 activation suggesting another mode of Cu-mediated MEK1 activation that is yet to be characterized. These results suggest that MEK1 is a metal-sensitive enzyme and that targeting these metals may be exploited to inhibit MAPK signaling for therapy.