Unusual α-Carbon Hydroxylation of Proline Promotes Active-Site Maturation.
Τίτλος | Unusual α-Carbon Hydroxylation of Proline Promotes Active-Site Maturation. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | 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. |
Journal | J Am Chem Soc |
Volume | 139 |
Issue | 15 |
Pagination | 5330-5337 |
Date Published | 2017 04 19 |
ISSN | 1520-5126 |
Λέξεις κλειδιά | Amidohydrolases, Bacillus anthracis, Bacillus cereus, Binding Sites, Carbon, Crystallography, X-Ray, Hydrogen Bonding, Hydroxylation, Models, Molecular, Proline |
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 C 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. |
DOI | 10.1021/jacs.6b12209 |
Alternate Journal | J. Am. Chem. Soc. |
PubMed ID | 28333455 |