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Representations of structures of the ternary complexes of E. coli DHFR with NADPH and folate with the M20 loop in the open (A) and closed (B) conformation (Sawaya and Kraut 1997). Met 20 is indicated, which in the open complex points away from the active site, but blocks access to N5 of the substrate in the closed form. Residues Asp 27 and Trp 22 together with substrate provide a binding site for water.
