Differential active site loop conformations mediate promiscuous activities in the lactonase SsoPox.

Enzymes are proficient catalysts that enable fast rates of Michaelis-complex formation, the chemical step and products release. These different steps may require different conformational states of the active site that have distinct binding properties. Moreover, the conformational flexibility of the...

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Autores principales:	Julien Hiblot, Guillaume Gotthard, Mikael Elias, Eric Chabriere
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/076e310a0a9341e4b1de414da4202dfe
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spelling	oai:doaj.org-article:076e310a0a9341e4b1de414da4202dfe2021-11-18T08:54:10ZDifferential active site loop conformations mediate promiscuous activities in the lactonase SsoPox.1932-620310.1371/journal.pone.0075272https://doaj.org/article/076e310a0a9341e4b1de414da4202dfe2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24086491/?tool=EBIhttps://doaj.org/toc/1932-6203Enzymes are proficient catalysts that enable fast rates of Michaelis-complex formation, the chemical step and products release. These different steps may require different conformational states of the active site that have distinct binding properties. Moreover, the conformational flexibility of the active site mediates alternative, promiscuous functions. Here we focused on the lactonase SsoPox from Sulfolobus solfataricus. SsoPox is a native lactonase endowed with promiscuous phosphotriesterase activity. We identified a position in the active site loop (W263) that governs its flexibility, and thereby affects the substrate specificity of the enzyme. We isolated two different sets of substitutions at position 263 that induce two distinct conformational sampling of the active loop and characterized the structural and kinetic effects of these substitutions. These sets of mutations selectively and distinctly mediate the improvement of the promiscuous phosphotriesterase and oxo-lactonase activities of SsoPox by increasing active-site loop flexibility. These observations corroborate the idea that conformational diversity governs enzymatic promiscuity and is a key feature of protein evolvability.Julien HiblotGuillaume GotthardMikael EliasEric ChabrierePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e75272 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Julien Hiblot Guillaume Gotthard Mikael Elias Eric Chabriere Differential active site loop conformations mediate promiscuous activities in the lactonase SsoPox.
description	Enzymes are proficient catalysts that enable fast rates of Michaelis-complex formation, the chemical step and products release. These different steps may require different conformational states of the active site that have distinct binding properties. Moreover, the conformational flexibility of the active site mediates alternative, promiscuous functions. Here we focused on the lactonase SsoPox from Sulfolobus solfataricus. SsoPox is a native lactonase endowed with promiscuous phosphotriesterase activity. We identified a position in the active site loop (W263) that governs its flexibility, and thereby affects the substrate specificity of the enzyme. We isolated two different sets of substitutions at position 263 that induce two distinct conformational sampling of the active loop and characterized the structural and kinetic effects of these substitutions. These sets of mutations selectively and distinctly mediate the improvement of the promiscuous phosphotriesterase and oxo-lactonase activities of SsoPox by increasing active-site loop flexibility. These observations corroborate the idea that conformational diversity governs enzymatic promiscuity and is a key feature of protein evolvability.
format	article
author	Julien Hiblot Guillaume Gotthard Mikael Elias Eric Chabriere
author_facet	Julien Hiblot Guillaume Gotthard Mikael Elias Eric Chabriere
author_sort	Julien Hiblot
title	Differential active site loop conformations mediate promiscuous activities in the lactonase SsoPox.
title_short	Differential active site loop conformations mediate promiscuous activities in the lactonase SsoPox.
title_full	Differential active site loop conformations mediate promiscuous activities in the lactonase SsoPox.
title_fullStr	Differential active site loop conformations mediate promiscuous activities in the lactonase SsoPox.
title_full_unstemmed	Differential active site loop conformations mediate promiscuous activities in the lactonase SsoPox.
title_sort	differential active site loop conformations mediate promiscuous activities in the lactonase ssopox.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/076e310a0a9341e4b1de414da4202dfe
work_keys_str_mv	AT julienhiblot differentialactivesiteloopconformationsmediatepromiscuousactivitiesinthelactonasessopox AT guillaumegotthard differentialactivesiteloopconformationsmediatepromiscuousactivitiesinthelactonasessopox AT mikaelelias differentialactivesiteloopconformationsmediatepromiscuousactivitiesinthelactonasessopox AT ericchabriere differentialactivesiteloopconformationsmediatepromiscuousactivitiesinthelactonasessopox
_version_	1718421185065123840

Differential active site loop conformations mediate promiscuous activities in the lactonase SsoPox.

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