A Peptide-Induced Self-Cleavage Reaction Initiates the Activation of Tyrosinase.

Ioannis Kampatsikas, Aleksandar Bijelic, Matthias Pretzler, Annette Rompel

Angewandte Chemie (International ed. in English) 2019 May 27

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The conversion of inactive pro-polyphenol oxidases (pro-PPOs) into the active enzyme results from the proteolytic cleavage of its C-terminal domain. Herein, a peptide-mediated cleavage process that activates pro-MdPPO1 (Malus domestica) is reported. Mass spectrometry, mutagenesis studies, and X-ray crystal-structure analysis of pro-MdPPO1 (1.35 Å) and two separated C-terminal domains, one obtained upon self-cleavage of pro-MdPPO1 and the other one produced independently, were applied to study the observed self-cleavage. The sequence Lys 355-Val 370 located in the linker between the active and the C-terminal domain is indispensable for the self-cleavage. Partial introduction (Lys 352-Ala 360) of this peptide into the sequence of two other PPOs, MdPPO2 and aurone synthase (CgAUS1), triggered self-cleavage in the resulting mutants. This is the first experimental proof of a self-cleavage-inducing peptide in PPOs, unveiling a new mode of activation for this enzyme class that is independent of any external protease. © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Citation

Ioannis Kampatsikas, Aleksandar Bijelic, Matthias Pretzler, Annette Rompel. A Peptide-Induced Self-Cleavage Reaction Initiates the Activation of Tyrosinase. Angewandte Chemie (International ed. in English). 2019 May 27;58(22):7475-7479