Focused Proteomics Analysis of Habu Snake (Protobothrops flavoviridis) Venom Using Antivenom-Based Affinity Chromatography Reveals Novel Myonecrosis-Enhancing Activity of Thrombin-Like Serine Proteases

Snakebites are one of the major causes of death and long-term disability in the developing countries due to the presence of various bioactive peptides and proteins in snake venom. In Japan, the venom of the habu snake (Protobothrops flavoviridis) causes severe permanent damage due to its myonecrotic...

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Autores principales:	Tomohisa Ogawa, Yu Tobishima, Shizuka Kamata, Youhei Matsuda, Koji Muramoto, Masafumi Hidaka, Eugene Futai, Takeshi Kuraishi, Shinichi Yokota, Motonori Ohno, Shosaku Hattori
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	antivenom myonecrosis phospholipase A2 proteomics pseudoenzyme serine protease Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/1b5bc815ca7b497a83438b3238f5b721
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spelling	oai:doaj.org-article:1b5bc815ca7b497a83438b3238f5b7212021-11-04T05:51:28ZFocused Proteomics Analysis of Habu Snake (Protobothrops flavoviridis) Venom Using Antivenom-Based Affinity Chromatography Reveals Novel Myonecrosis-Enhancing Activity of Thrombin-Like Serine Proteases1663-981210.3389/fphar.2021.766406https://doaj.org/article/1b5bc815ca7b497a83438b3238f5b7212021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.766406/fullhttps://doaj.org/toc/1663-9812Snakebites are one of the major causes of death and long-term disability in the developing countries due to the presence of various bioactive peptides and proteins in snake venom. In Japan, the venom of the habu snake (Protobothrops flavoviridis) causes severe permanent damage due to its myonecrotic toxins. Antivenom immunoglobulins are an effective therapy for snakebites, and antivenom was recently developed with effective suppressive activity against myonecrosis induced by snake venom. To compare the properties of an antivenom having anti-myonecrotic activity with those of conventional antivenom with no anti-myonecrotic activity, this study applied focused proteomics analysis of habu venom proteins using 2D gel electrophoresis. As a target protein for antivenom immunoglobulins with anti-myonecrotic activity, we identified a thrombin-like serine protease, TLSP2 (TLf2), which was an inactive proteolytic isoform due to the replacement of the active site, His43 with Arg. Additionally, we identified the unique properties and a novel synergistic function of pseudoenzyme TLf2 as a myonecrosis-enhancing factor. To our knowledge, this is the first report of a function of a catalytically inactive snake serine protease.Tomohisa OgawaTomohisa OgawaYu TobishimaShizuka KamataYouhei MatsudaKoji MuramotoMasafumi HidakaEugene FutaiTakeshi KuraishiShinichi YokotaMotonori OhnoShosaku HattoriFrontiers Media S.A.articleantivenommyonecrosisphospholipase A2proteomicspseudoenzymeserine proteaseTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	antivenom myonecrosis phospholipase A2 proteomics pseudoenzyme serine protease Therapeutics. Pharmacology RM1-950
spellingShingle	antivenom myonecrosis phospholipase A2 proteomics pseudoenzyme serine protease Therapeutics. Pharmacology RM1-950 Tomohisa Ogawa Tomohisa Ogawa Yu Tobishima Shizuka Kamata Youhei Matsuda Koji Muramoto Masafumi Hidaka Eugene Futai Takeshi Kuraishi Shinichi Yokota Motonori Ohno Shosaku Hattori Focused Proteomics Analysis of Habu Snake (Protobothrops flavoviridis) Venom Using Antivenom-Based Affinity Chromatography Reveals Novel Myonecrosis-Enhancing Activity of Thrombin-Like Serine Proteases
description	Snakebites are one of the major causes of death and long-term disability in the developing countries due to the presence of various bioactive peptides and proteins in snake venom. In Japan, the venom of the habu snake (Protobothrops flavoviridis) causes severe permanent damage due to its myonecrotic toxins. Antivenom immunoglobulins are an effective therapy for snakebites, and antivenom was recently developed with effective suppressive activity against myonecrosis induced by snake venom. To compare the properties of an antivenom having anti-myonecrotic activity with those of conventional antivenom with no anti-myonecrotic activity, this study applied focused proteomics analysis of habu venom proteins using 2D gel electrophoresis. As a target protein for antivenom immunoglobulins with anti-myonecrotic activity, we identified a thrombin-like serine protease, TLSP2 (TLf2), which was an inactive proteolytic isoform due to the replacement of the active site, His43 with Arg. Additionally, we identified the unique properties and a novel synergistic function of pseudoenzyme TLf2 as a myonecrosis-enhancing factor. To our knowledge, this is the first report of a function of a catalytically inactive snake serine protease.
format	article
author	Tomohisa Ogawa Tomohisa Ogawa Yu Tobishima Shizuka Kamata Youhei Matsuda Koji Muramoto Masafumi Hidaka Eugene Futai Takeshi Kuraishi Shinichi Yokota Motonori Ohno Shosaku Hattori
author_facet	Tomohisa Ogawa Tomohisa Ogawa Yu Tobishima Shizuka Kamata Youhei Matsuda Koji Muramoto Masafumi Hidaka Eugene Futai Takeshi Kuraishi Shinichi Yokota Motonori Ohno Shosaku Hattori
author_sort	Tomohisa Ogawa
title	Focused Proteomics Analysis of Habu Snake (Protobothrops flavoviridis) Venom Using Antivenom-Based Affinity Chromatography Reveals Novel Myonecrosis-Enhancing Activity of Thrombin-Like Serine Proteases
title_short	Focused Proteomics Analysis of Habu Snake (Protobothrops flavoviridis) Venom Using Antivenom-Based Affinity Chromatography Reveals Novel Myonecrosis-Enhancing Activity of Thrombin-Like Serine Proteases
title_full	Focused Proteomics Analysis of Habu Snake (Protobothrops flavoviridis) Venom Using Antivenom-Based Affinity Chromatography Reveals Novel Myonecrosis-Enhancing Activity of Thrombin-Like Serine Proteases
title_fullStr	Focused Proteomics Analysis of Habu Snake (Protobothrops flavoviridis) Venom Using Antivenom-Based Affinity Chromatography Reveals Novel Myonecrosis-Enhancing Activity of Thrombin-Like Serine Proteases
title_full_unstemmed	Focused Proteomics Analysis of Habu Snake (Protobothrops flavoviridis) Venom Using Antivenom-Based Affinity Chromatography Reveals Novel Myonecrosis-Enhancing Activity of Thrombin-Like Serine Proteases
title_sort	focused proteomics analysis of habu snake (protobothrops flavoviridis) venom using antivenom-based affinity chromatography reveals novel myonecrosis-enhancing activity of thrombin-like serine proteases
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/1b5bc815ca7b497a83438b3238f5b721
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Focused Proteomics Analysis of Habu Snake (Protobothrops flavoviridis) Venom Using Antivenom-Based Affinity Chromatography Reveals Novel Myonecrosis-Enhancing Activity of Thrombin-Like Serine Proteases

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