Tuning of thioredoxin redox properties by intramolecular hydrogen bonds.

Thioredoxin-like proteins contain a characteristic C-x-x-C active site motif and are involved in a large number of biological processes ranging from electron transfer, cellular redox level maintenance, and regulation of cellular processes. The mechanism for deprotonation of the buried C-terminal act...

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Autores principales:	Åsmund Kjendseth Røhr, Marta Hammerstad, K Kristoffer Andersson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dfe44617bb0d44f1817a2df9e1cf7a7c
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spelling	oai:doaj.org-article:dfe44617bb0d44f1817a2df9e1cf7a7c2021-11-18T09:03:17ZTuning of thioredoxin redox properties by intramolecular hydrogen bonds.1932-620310.1371/journal.pone.0069411https://doaj.org/article/dfe44617bb0d44f1817a2df9e1cf7a7c2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23936007/?tool=EBIhttps://doaj.org/toc/1932-6203Thioredoxin-like proteins contain a characteristic C-x-x-C active site motif and are involved in a large number of biological processes ranging from electron transfer, cellular redox level maintenance, and regulation of cellular processes. The mechanism for deprotonation of the buried C-terminal active site cysteine in thioredoxin, necessary for dissociation of the mixed-disulfide intermediate that occurs under thiol/disulfide mediated electron transfer, is not well understood for all thioredoxin superfamily members. Here we have characterized a 8.7 kD thioredoxin (BC3987) from Bacillus cereus that unlike the typical thioredoxin appears to use the conserved Thr8 side chain near the unusual C-P-P-C active site to increase enzymatic activity by forming a hydrogen bond to the buried cysteine. Our hypothesis is based on biochemical assays and thiolate pKa titrations where the wild type and T8A mutant are compared, phylogenetic analysis of related thioredoxins, and QM/MM calculations with the BC3987 crystal structure as a precursor for modeling of reduced active sites. We suggest that our model applies to other thioredoxin subclasses with similar active site arrangements.Åsmund Kjendseth RøhrMarta HammerstadK Kristoffer AnderssonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e69411 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Åsmund Kjendseth Røhr Marta Hammerstad K Kristoffer Andersson Tuning of thioredoxin redox properties by intramolecular hydrogen bonds.
description	Thioredoxin-like proteins contain a characteristic C-x-x-C active site motif and are involved in a large number of biological processes ranging from electron transfer, cellular redox level maintenance, and regulation of cellular processes. The mechanism for deprotonation of the buried C-terminal active site cysteine in thioredoxin, necessary for dissociation of the mixed-disulfide intermediate that occurs under thiol/disulfide mediated electron transfer, is not well understood for all thioredoxin superfamily members. Here we have characterized a 8.7 kD thioredoxin (BC3987) from Bacillus cereus that unlike the typical thioredoxin appears to use the conserved Thr8 side chain near the unusual C-P-P-C active site to increase enzymatic activity by forming a hydrogen bond to the buried cysteine. Our hypothesis is based on biochemical assays and thiolate pKa titrations where the wild type and T8A mutant are compared, phylogenetic analysis of related thioredoxins, and QM/MM calculations with the BC3987 crystal structure as a precursor for modeling of reduced active sites. We suggest that our model applies to other thioredoxin subclasses with similar active site arrangements.
format	article
author	Åsmund Kjendseth Røhr Marta Hammerstad K Kristoffer Andersson
author_facet	Åsmund Kjendseth Røhr Marta Hammerstad K Kristoffer Andersson
author_sort	Åsmund Kjendseth Røhr
title	Tuning of thioredoxin redox properties by intramolecular hydrogen bonds.
title_short	Tuning of thioredoxin redox properties by intramolecular hydrogen bonds.
title_full	Tuning of thioredoxin redox properties by intramolecular hydrogen bonds.
title_fullStr	Tuning of thioredoxin redox properties by intramolecular hydrogen bonds.
title_full_unstemmed	Tuning of thioredoxin redox properties by intramolecular hydrogen bonds.
title_sort	tuning of thioredoxin redox properties by intramolecular hydrogen bonds.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/dfe44617bb0d44f1817a2df9e1cf7a7c
work_keys_str_mv	AT asmundkjendsethrøhr tuningofthioredoxinredoxpropertiesbyintramolecularhydrogenbonds AT martahammerstad tuningofthioredoxinredoxpropertiesbyintramolecularhydrogenbonds AT kkristofferandersson tuningofthioredoxinredoxpropertiesbyintramolecularhydrogenbonds
_version_	1718420995079929856

Tuning of thioredoxin redox properties by intramolecular hydrogen bonds.

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