Abnormal Enhancement of Protein Disulfide Isomerase-like Activity of a Cyclic Diselenide Conjugated with a Basic Amino Acid by Inserting a Glycine Spacer

In a previous study, we reported that (<i>S</i>)-1,2-diselenane-4-amine (<b>1</b>) catalyzes oxidative protein folding through protein disulfide isomerase (PDI)-like catalytic mechanisms and that the direct conjugation of a basic amino acid (Xaa: His, Lys, or Arg) via an amid...

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Autores principales:	Rumi Mikami, Shunsuke Tsukagoshi, Kenta Arai
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	oxidative folding enzyme model selenium aggregation chaperone catalyst Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e656d5c9b25349b4972e2576a98beacb
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spelling	oai:doaj.org-article:e656d5c9b25349b4972e2576a98beacb2021-11-25T16:46:55ZAbnormal Enhancement of Protein Disulfide Isomerase-like Activity of a Cyclic Diselenide Conjugated with a Basic Amino Acid by Inserting a Glycine Spacer10.3390/biology101110902079-7737https://doaj.org/article/e656d5c9b25349b4972e2576a98beacb2021-10-01T00:00:00Zhttps://www.mdpi.com/2079-7737/10/11/1090https://doaj.org/toc/2079-7737In a previous study, we reported that (<i>S</i>)-1,2-diselenane-4-amine (<b>1</b>) catalyzes oxidative protein folding through protein disulfide isomerase (PDI)-like catalytic mechanisms and that the direct conjugation of a basic amino acid (Xaa: His, Lys, or Arg) via an amide bond improves the catalytic activity of <b>1</b> by increasing its diselenide (Se–Se) reduction potential (<i>E</i>′°). In this study, to modulate the Se–Se redox properties and the association of the compounds with a protein substrate, new catalysts, in which a Gly spacer was inserted between <b>1</b> and Xaa, were synthesized. Exhaustive comparison of the PDI-like catalytic activities and <i>E</i>′° values among <b>1</b>, <b>1</b>-Xaa, and <b>1</b>-Gly-Xaa showed that the insertion of a Gly spacer into <b>1</b>-Xaa either did not change or slightly reduced the PDI-like activity and the <i>E</i>′° values. Importantly, however, only <b>1</b>-Gly-Arg deviated from this generality and showed obviously increased <i>E</i>°′ value and PDI-like activity compared to the corresponding compound with no Gly spacer (<b>1</b>-Arg); on the contrary, its catalytic activity was the highest among the diselenide compounds employed in this study, while this abnormal enhancement of the catalytic activity of <b>1</b>-Gly-Arg could not be fully explained by the thermodynamics of the Se–Se bond and its association ability with protein substrates.Rumi MikamiShunsuke TsukagoshiKenta AraiMDPI AGarticleoxidative foldingenzyme modelseleniumaggregationchaperonecatalystBiology (General)QH301-705.5ENBiology, Vol 10, Iss 1090, p 1090 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	oxidative folding enzyme model selenium aggregation chaperone catalyst Biology (General) QH301-705.5
spellingShingle	oxidative folding enzyme model selenium aggregation chaperone catalyst Biology (General) QH301-705.5 Rumi Mikami Shunsuke Tsukagoshi Kenta Arai Abnormal Enhancement of Protein Disulfide Isomerase-like Activity of a Cyclic Diselenide Conjugated with a Basic Amino Acid by Inserting a Glycine Spacer
description	In a previous study, we reported that (<i>S</i>)-1,2-diselenane-4-amine (<b>1</b>) catalyzes oxidative protein folding through protein disulfide isomerase (PDI)-like catalytic mechanisms and that the direct conjugation of a basic amino acid (Xaa: His, Lys, or Arg) via an amide bond improves the catalytic activity of <b>1</b> by increasing its diselenide (Se–Se) reduction potential (<i>E</i>′°). In this study, to modulate the Se–Se redox properties and the association of the compounds with a protein substrate, new catalysts, in which a Gly spacer was inserted between <b>1</b> and Xaa, were synthesized. Exhaustive comparison of the PDI-like catalytic activities and <i>E</i>′° values among <b>1</b>, <b>1</b>-Xaa, and <b>1</b>-Gly-Xaa showed that the insertion of a Gly spacer into <b>1</b>-Xaa either did not change or slightly reduced the PDI-like activity and the <i>E</i>′° values. Importantly, however, only <b>1</b>-Gly-Arg deviated from this generality and showed obviously increased <i>E</i>°′ value and PDI-like activity compared to the corresponding compound with no Gly spacer (<b>1</b>-Arg); on the contrary, its catalytic activity was the highest among the diselenide compounds employed in this study, while this abnormal enhancement of the catalytic activity of <b>1</b>-Gly-Arg could not be fully explained by the thermodynamics of the Se–Se bond and its association ability with protein substrates.
format	article
author	Rumi Mikami Shunsuke Tsukagoshi Kenta Arai
author_facet	Rumi Mikami Shunsuke Tsukagoshi Kenta Arai
author_sort	Rumi Mikami
title	Abnormal Enhancement of Protein Disulfide Isomerase-like Activity of a Cyclic Diselenide Conjugated with a Basic Amino Acid by Inserting a Glycine Spacer
title_short	Abnormal Enhancement of Protein Disulfide Isomerase-like Activity of a Cyclic Diselenide Conjugated with a Basic Amino Acid by Inserting a Glycine Spacer
title_full	Abnormal Enhancement of Protein Disulfide Isomerase-like Activity of a Cyclic Diselenide Conjugated with a Basic Amino Acid by Inserting a Glycine Spacer
title_fullStr	Abnormal Enhancement of Protein Disulfide Isomerase-like Activity of a Cyclic Diselenide Conjugated with a Basic Amino Acid by Inserting a Glycine Spacer
title_full_unstemmed	Abnormal Enhancement of Protein Disulfide Isomerase-like Activity of a Cyclic Diselenide Conjugated with a Basic Amino Acid by Inserting a Glycine Spacer
title_sort	abnormal enhancement of protein disulfide isomerase-like activity of a cyclic diselenide conjugated with a basic amino acid by inserting a glycine spacer
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e656d5c9b25349b4972e2576a98beacb
work_keys_str_mv	AT rumimikami abnormalenhancementofproteindisulfideisomeraselikeactivityofacyclicdiselenideconjugatedwithabasicaminoacidbyinsertingaglycinespacer AT shunsuketsukagoshi abnormalenhancementofproteindisulfideisomeraselikeactivityofacyclicdiselenideconjugatedwithabasicaminoacidbyinsertingaglycinespacer AT kentaarai abnormalenhancementofproteindisulfideisomeraselikeactivityofacyclicdiselenideconjugatedwithabasicaminoacidbyinsertingaglycinespacer
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Abnormal Enhancement of Protein Disulfide Isomerase-like Activity of a Cyclic Diselenide Conjugated with a Basic Amino Acid by Inserting a Glycine Spacer

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