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; Michael Kokkinidis

doi:10.1021/jacs.6b12209

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)

Molecular Microbiology

Research output: Contribution to journal › Article › peer-review

20 Citations (Scopus)

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_α 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 language	English
Pages (from-to)	5330-5337
Number of pages	8
Journal	Journal of the American Chemical Society
Volume	139
Issue number	15
Early online date	23 Mar 2017
DOIs	https://doi.org/10.1021/jacs.6b12209
Publication status	Published - 19 Apr 2017

ASJC Scopus subject areas

Catalysis
General Chemistry
Biochemistry
Colloid and Surface Chemistry

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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

@article{e4c74769e2d94f819480dacde178cb9a,

title = "Unusual α-Carbon Hydroxylation of Proline Promotes Active-Site Maturation",

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.",

author = "Fadouloglou, {Vasiliki E.} and Stavroula Balomenou and Michalis Aivaliotis and Dina Kotsifaki and Sofia Arnaouteli and Anastasia Tomatsidou and Giorgos Efstathiou and Nikos Kountourakis and Sofia Miliara and Marianna Griniezaki and Aleka Tsalafouta and Pergantis, {Spiros A.} and Boneca, {Ivo G.} and Glykos, {Nicholas M.} and Vassilis Bouriotis and Michael Kokkinidis",

note = "This work was supported by the EU/FP7 project InnovCrete and the GSRT projects SYN11_1_31, SYN11_3_1321, THALIS, and 12CHN396.",

year = "2017",

month = apr,

day = "19",

doi = "10.1021/jacs.6b12209",

language = "English",

volume = "139",

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Fadouloglou, VE, Balomenou, S, Aivaliotis, M, Kotsifaki, D, Arnaouteli, S, Tomatsidou, A, Efstathiou, G, Kountourakis, N, Miliara, S, Griniezaki, M, Tsalafouta, A, Pergantis, SA, Boneca, IG, Glykos, NM, Bouriotis, V & Kokkinidis, M 2017, 'Unusual α-Carbon Hydroxylation of Proline Promotes Active-Site Maturation', Journal of the American Chemical Society, vol. 139, no. 15, pp. 5330-5337. https://doi.org/10.1021/jacs.6b12209

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.

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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 -

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

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