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Structural basis for substrate discrimination. (a) In the model of lariat RNA bound to Dbr1, His91 is well-positioned to act as a catalytic acid and the metal-associated water molecule as the nucleophile in the hydrolysis of the 2′,5′-phosphodiester linkage. (b) In the AK51•Dbr1 co-structure, fortuitous binding of a 3′,5′-phosphodiester linkage reveals that the putative catalytic acid is displaced from the active site by the 2′ hydroxyl moiety, preventing hydrolysis of the RNA.
