Unusual α-Carbon Hydroxylation of Proline Promotes Active-Site Maturation

Vasiliki E. Fadouloglou, Stavroula Balomenou, Michalis Aivaliotis, Dina Kotsifaki, Sofia Arnaouteli, Anastasia Tomatsidou, Giorgos Efstathiou, Nikos Kountourakis, Sofia Miliara, Marianna Griniezaki, Aleka Tsalafouta, Spiros A. Pergantis, Ivo G. Boneca, Nicholas M. Glykos, Vassilis Bouriotis (Lead / Corresponding author), Michael Kokkinidis (Lead / Corresponding author)

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Abstract

The full extent of proline (Pro) hydroxylation has yet to be established, as it is largely unexplored in bacteria. We describe here a so far unknown Pro hydroxylation activity which occurs in active sites of polysaccharide deacetylases (PDAs) from bacterial pathogens, modifying the protein backbone at the Cα atom of a Pro residue to produce 2-hydroxyproline (2-Hyp). This process modifies with high specificity a conserved Pro, shares with the deacetylation reaction the same active site and one catalytic residue, and utilizes molecular oxygen as source for the hydroxyl group oxygen of 2-Hyp. By providing additional hydrogen-bonding capacity, the Pro→2-Hyp conversion alters the active site and enhances significantly deacetylase activity, probably by creating a more favorable environment for transition-state stabilization. Our results classify this process as an active-site “maturation”, which is highly atypical in being a protein backbone-modifying activity, rather than a side-chain-modifying one.

Original languageEnglish
Pages (from-to)5330-5337
Number of pages8
JournalJournal of the American Chemical Society
Volume139
Issue number15
Early online date23 Mar 2017
DOIs
Publication statusPublished - 19 Apr 2017

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Fadouloglou, V. E., Balomenou, S., Aivaliotis, M., Kotsifaki, D., Arnaouteli, S., Tomatsidou, A., Efstathiou, G., Kountourakis, N., Miliara, S., Griniezaki, M., Tsalafouta, A., Pergantis, S. A., Boneca, I. G., Glykos, N. M., Bouriotis, V., & Kokkinidis, M. (2017). Unusual α-Carbon Hydroxylation of Proline Promotes Active-Site Maturation. Journal of the American Chemical Society, 139(15), 5330-5337. https://doi.org/10.1021/jacs.6b12209