Enzyme characteristics of pathogen-specific trehalose-6-phosphate phosphatases

Abstract Owing to the key role of trehalose in pathogenic organisms, there has recently been growing interest in trehalose metabolism for therapeutic purposes. Trehalose-6-phosphate phosphatase (TPP) is a pivotal enzyme in the most prominent biosynthesis pathway (OtsAB). Here, we compare the enzyme...

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Autores principales:	Megan Cross, Siji Rajan, Janine Chekaiban, Jake Saunders, Chloe Hamilton, Jeong-Sun Kim, Mark J. Coster, Robin B. Gasser, Andreas Hofmann
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d836d5dfbaf740808ada4988984968f9
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spelling	oai:doaj.org-article:d836d5dfbaf740808ada4988984968f92021-12-02T16:06:51ZEnzyme characteristics of pathogen-specific trehalose-6-phosphate phosphatases10.1038/s41598-017-02220-22045-2322https://doaj.org/article/d836d5dfbaf740808ada4988984968f92017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02220-2https://doaj.org/toc/2045-2322Abstract Owing to the key role of trehalose in pathogenic organisms, there has recently been growing interest in trehalose metabolism for therapeutic purposes. Trehalose-6-phosphate phosphatase (TPP) is a pivotal enzyme in the most prominent biosynthesis pathway (OtsAB). Here, we compare the enzyme characteristics of recombinant TPPs from five important nematode and bacterial pathogens, including three novel members of this protein family. Analysis of the kinetics of trehalose-6-phosphate hydrolysis reveals that all five enzymes display a burst-like kinetic behaviour which is characterised by a decrease of the enzymatic rate after the pre-steady state. The observed super-stoichiometric burst amplitudes can be explained by multiple global conformational changes in members of this enzyme family during substrate processing. In the search for specific TPP inhibitors, the trapping of the complex conformational transitions in TPPs during the catalytic cycle may present a worthwhile strategy to explore.Megan CrossSiji RajanJanine ChekaibanJake SaundersChloe HamiltonJeong-Sun KimMark J. CosterRobin B. GasserAndreas HofmannNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Megan Cross Siji Rajan Janine Chekaiban Jake Saunders Chloe Hamilton Jeong-Sun Kim Mark J. Coster Robin B. Gasser Andreas Hofmann Enzyme characteristics of pathogen-specific trehalose-6-phosphate phosphatases
description	Abstract Owing to the key role of trehalose in pathogenic organisms, there has recently been growing interest in trehalose metabolism for therapeutic purposes. Trehalose-6-phosphate phosphatase (TPP) is a pivotal enzyme in the most prominent biosynthesis pathway (OtsAB). Here, we compare the enzyme characteristics of recombinant TPPs from five important nematode and bacterial pathogens, including three novel members of this protein family. Analysis of the kinetics of trehalose-6-phosphate hydrolysis reveals that all five enzymes display a burst-like kinetic behaviour which is characterised by a decrease of the enzymatic rate after the pre-steady state. The observed super-stoichiometric burst amplitudes can be explained by multiple global conformational changes in members of this enzyme family during substrate processing. In the search for specific TPP inhibitors, the trapping of the complex conformational transitions in TPPs during the catalytic cycle may present a worthwhile strategy to explore.
format	article
author	Megan Cross Siji Rajan Janine Chekaiban Jake Saunders Chloe Hamilton Jeong-Sun Kim Mark J. Coster Robin B. Gasser Andreas Hofmann
author_facet	Megan Cross Siji Rajan Janine Chekaiban Jake Saunders Chloe Hamilton Jeong-Sun Kim Mark J. Coster Robin B. Gasser Andreas Hofmann
author_sort	Megan Cross
title	Enzyme characteristics of pathogen-specific trehalose-6-phosphate phosphatases
title_short	Enzyme characteristics of pathogen-specific trehalose-6-phosphate phosphatases
title_full	Enzyme characteristics of pathogen-specific trehalose-6-phosphate phosphatases
title_fullStr	Enzyme characteristics of pathogen-specific trehalose-6-phosphate phosphatases
title_full_unstemmed	Enzyme characteristics of pathogen-specific trehalose-6-phosphate phosphatases
title_sort	enzyme characteristics of pathogen-specific trehalose-6-phosphate phosphatases
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d836d5dfbaf740808ada4988984968f9
work_keys_str_mv	AT megancross enzymecharacteristicsofpathogenspecifictrehalose6phosphatephosphatases AT sijirajan enzymecharacteristicsofpathogenspecifictrehalose6phosphatephosphatases AT janinechekaiban enzymecharacteristicsofpathogenspecifictrehalose6phosphatephosphatases AT jakesaunders enzymecharacteristicsofpathogenspecifictrehalose6phosphatephosphatases AT chloehamilton enzymecharacteristicsofpathogenspecifictrehalose6phosphatephosphatases AT jeongsunkim enzymecharacteristicsofpathogenspecifictrehalose6phosphatephosphatases AT markjcoster enzymecharacteristicsofpathogenspecifictrehalose6phosphatephosphatases AT robinbgasser enzymecharacteristicsofpathogenspecifictrehalose6phosphatephosphatases AT andreashofmann enzymecharacteristicsofpathogenspecifictrehalose6phosphatephosphatases
_version_	1718384871602126848

Enzyme characteristics of pathogen-specific trehalose-6-phosphate phosphatases

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