Table S1 - A Model of a MAPK•Substrate Complex in an Active Conformation: A Computational and Experimental Approach

Distance constraints between Lig-D and ERK2 were set based on the known interactions of the two motifs (RR and ΦA-X-ΦB) with phosphatase (PDB ID: 2GPH). Distance constraints between Lig-F and ERK2 were set to make the Phe-Xaa-Phe motif (DEF motif) binding a hydrophobic pocket formed between the P+1 site, the αF helix and the MAP kinase insert. The binding constraints for Ets(1-42) were imposed to enforce the hydrogen bonding interactions between Thr residue in the Thr-Pro motif with Asp-147 and Lys-149 of ERK2. In addition, the proline in the Thr-Pro motif was restrained to adopt a similar binding mode to that in Ser-Pro motif of HHASPRK bound to the cyclin-dependent kinase (CDK2) (PDB ID: 1QMZ). (DOCX)