TY - JOUR
T1 - Unusual α-Carbon Hydroxylation of Proline Promotes Active-Site Maturation
AU - Fadouloglou, Vasiliki E.
AU - Balomenou, Stavroula
AU - Aivaliotis, Michalis
AU - Kotsifaki, Dina
AU - Arnaouteli, Sofia
AU - Tomatsidou, Anastasia
AU - Efstathiou, Giorgos
AU - Kountourakis, Nikos
AU - Miliara, Sofia
AU - Griniezaki, Marianna
AU - Tsalafouta, Aleka
AU - Pergantis, Spiros A.
AU - Boneca, Ivo G.
AU - Glykos, Nicholas M.
AU - Bouriotis, Vassilis
AU - Kokkinidis, Michael
N1 - This work was supported by the EU/FP7 project InnovCrete and the GSRT projects SYN11_1_31, SYN11_3_1321, THALIS, and 12CHN396.
PY - 2017/4/19
Y1 - 2017/4/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85017764997&partnerID=8YFLogxK
U2 - 10.1021/jacs.6b12209
DO - 10.1021/jacs.6b12209
M3 - Article
C2 - 28333455
SN - 0002-7863
VL - 139
SP - 5330
EP - 5337
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 15
ER -