Inhibition of Clostridium difficile TcdA and TcdB toxins with transition state analogues

The Clostridium difficile virulence factors TcdA and TcdB contain a glucosyltransferase domain (GTD), which has both glucohydrolase (GH) and glucosyltransferase (GT) activities. Here, the authors characterize the transition state features of the TcdA and TcdB GH reactions by measuring kinetic isotop...

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Autores principales:	Ashleigh S. Paparella, Briana L. Aboulache, Rajesh K. Harijan, Kathryn S. Potts, Peter C. Tyler, Vern L. Schramm
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Science Q
Acceso en línea:	https://doaj.org/article/2db89135c8f8435582d1f2cd71ae72c8
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spelling	oai:doaj.org-article:2db89135c8f8435582d1f2cd71ae72c82021-11-08T11:08:55ZInhibition of Clostridium difficile TcdA and TcdB toxins with transition state analogues10.1038/s41467-021-26580-62041-1723https://doaj.org/article/2db89135c8f8435582d1f2cd71ae72c82021-11-01T00:00:00Zhttps://doi.org/10.1038/s41467-021-26580-6https://doaj.org/toc/2041-1723The Clostridium difficile virulence factors TcdA and TcdB contain a glucosyltransferase domain (GTD), which has both glucohydrolase (GH) and glucosyltransferase (GT) activities. Here, the authors characterize the transition state features of the TcdA and TcdB GH reactions by measuring kinetic isotope effects and they identify two transition state analogues, isofagomine and noeuromycin that inhibit TcdA and TcdB. They also present the crystal structures of TcdB-GTD bound to these inhibitors and the reaction product UDP.Ashleigh S. PaparellaBriana L. AboulacheRajesh K. HarijanKathryn S. PottsPeter C. TylerVern L. SchrammNature PortfolioarticleScienceQENNature Communications, Vol 12, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Science Q
spellingShingle	Science Q Ashleigh S. Paparella Briana L. Aboulache Rajesh K. Harijan Kathryn S. Potts Peter C. Tyler Vern L. Schramm Inhibition of Clostridium difficile TcdA and TcdB toxins with transition state analogues
description	The Clostridium difficile virulence factors TcdA and TcdB contain a glucosyltransferase domain (GTD), which has both glucohydrolase (GH) and glucosyltransferase (GT) activities. Here, the authors characterize the transition state features of the TcdA and TcdB GH reactions by measuring kinetic isotope effects and they identify two transition state analogues, isofagomine and noeuromycin that inhibit TcdA and TcdB. They also present the crystal structures of TcdB-GTD bound to these inhibitors and the reaction product UDP.
format	article
author	Ashleigh S. Paparella Briana L. Aboulache Rajesh K. Harijan Kathryn S. Potts Peter C. Tyler Vern L. Schramm
author_facet	Ashleigh S. Paparella Briana L. Aboulache Rajesh K. Harijan Kathryn S. Potts Peter C. Tyler Vern L. Schramm
author_sort	Ashleigh S. Paparella
title	Inhibition of Clostridium difficile TcdA and TcdB toxins with transition state analogues
title_short	Inhibition of Clostridium difficile TcdA and TcdB toxins with transition state analogues
title_full	Inhibition of Clostridium difficile TcdA and TcdB toxins with transition state analogues
title_fullStr	Inhibition of Clostridium difficile TcdA and TcdB toxins with transition state analogues
title_full_unstemmed	Inhibition of Clostridium difficile TcdA and TcdB toxins with transition state analogues
title_sort	inhibition of clostridium difficile tcda and tcdb toxins with transition state analogues
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2db89135c8f8435582d1f2cd71ae72c8
work_keys_str_mv	AT ashleighspaparella inhibitionofclostridiumdifficiletcdaandtcdbtoxinswithtransitionstateanalogues AT brianalaboulache inhibitionofclostridiumdifficiletcdaandtcdbtoxinswithtransitionstateanalogues AT rajeshkharijan inhibitionofclostridiumdifficiletcdaandtcdbtoxinswithtransitionstateanalogues AT kathrynspotts inhibitionofclostridiumdifficiletcdaandtcdbtoxinswithtransitionstateanalogues AT peterctyler inhibitionofclostridiumdifficiletcdaandtcdbtoxinswithtransitionstateanalogues AT vernlschramm inhibitionofclostridiumdifficiletcdaandtcdbtoxinswithtransitionstateanalogues
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Inhibition of Clostridium difficile TcdA and TcdB toxins with transition state analogues

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