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Proposed autoproteolytic mechanism of ThnT. (A) The precleavage conformation shown in Fig. 5B. Dashed lines represent hydrogen bonds critical to activation of the system. A fourth hydrogen bond exists for Wat4, enabling it to shuttle the labile proton on T282 into solvent. (B) The amine leaving group is protonated by Wat3 and expelled, generating a planar ester. (C) The nucleophilic Wat3 is activated by the nascent amine and hydrolyzes the ester.
