Structural and Biochemical Characterization of Apicomplexan Inorganic Pyrophosphatases

Abstract Inorganic pyrophosphatases (PPase) participate in energy cycling and they are essential for growth and survival of organisms. Here we report extensive structural and functional characterization of soluble PPases from the human parasites Plasmodium falciparum (PfPPase) and Toxoplasma gondii...

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Autores principales:	Abhishek Jamwal, Manickam Yogavel, Malik. Z. Abdin, Swatantra. K. Jain, Amit Sharma
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4628c75d182f4e7996d49b30de5f982a
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spelling	oai:doaj.org-article:4628c75d182f4e7996d49b30de5f982a2021-12-02T12:31:47ZStructural and Biochemical Characterization of Apicomplexan Inorganic Pyrophosphatases10.1038/s41598-017-05234-y2045-2322https://doaj.org/article/4628c75d182f4e7996d49b30de5f982a2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05234-yhttps://doaj.org/toc/2045-2322Abstract Inorganic pyrophosphatases (PPase) participate in energy cycling and they are essential for growth and survival of organisms. Here we report extensive structural and functional characterization of soluble PPases from the human parasites Plasmodium falciparum (PfPPase) and Toxoplasma gondii (TgPPase). Our results show that PfPPase is a cytosolic enzyme whose gene expression is upregulated during parasite asexual stages. Cambialistic PfPPase actively hydrolyzes linear short chain polyphosphates like PPi, polyP3 and ATP in the presence of Zn2+. A remarkable new feature of PfPPase is the low complexity asparagine-rich N-terminal region that mediates its dimerization. Deletion of N-region has an unexpected and substantial effect on the stability of PfPPase domain, resulting in aggregation and significant loss of enzyme activity. Significantly, the crystal structures of PfPPase and TgPPase reveal unusual and unprecedented dimeric organizations and provide new fundamental insights into the variety of oligomeric assemblies possible in eukaryotic inorganic PPases.Abhishek JamwalManickam YogavelMalik. Z. AbdinSwatantra. K. JainAmit SharmaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Abhishek Jamwal Manickam Yogavel Malik. Z. Abdin Swatantra. K. Jain Amit Sharma Structural and Biochemical Characterization of Apicomplexan Inorganic Pyrophosphatases
description	Abstract Inorganic pyrophosphatases (PPase) participate in energy cycling and they are essential for growth and survival of organisms. Here we report extensive structural and functional characterization of soluble PPases from the human parasites Plasmodium falciparum (PfPPase) and Toxoplasma gondii (TgPPase). Our results show that PfPPase is a cytosolic enzyme whose gene expression is upregulated during parasite asexual stages. Cambialistic PfPPase actively hydrolyzes linear short chain polyphosphates like PPi, polyP3 and ATP in the presence of Zn2+. A remarkable new feature of PfPPase is the low complexity asparagine-rich N-terminal region that mediates its dimerization. Deletion of N-region has an unexpected and substantial effect on the stability of PfPPase domain, resulting in aggregation and significant loss of enzyme activity. Significantly, the crystal structures of PfPPase and TgPPase reveal unusual and unprecedented dimeric organizations and provide new fundamental insights into the variety of oligomeric assemblies possible in eukaryotic inorganic PPases.
format	article
author	Abhishek Jamwal Manickam Yogavel Malik. Z. Abdin Swatantra. K. Jain Amit Sharma
author_facet	Abhishek Jamwal Manickam Yogavel Malik. Z. Abdin Swatantra. K. Jain Amit Sharma
author_sort	Abhishek Jamwal
title	Structural and Biochemical Characterization of Apicomplexan Inorganic Pyrophosphatases
title_short	Structural and Biochemical Characterization of Apicomplexan Inorganic Pyrophosphatases
title_full	Structural and Biochemical Characterization of Apicomplexan Inorganic Pyrophosphatases
title_fullStr	Structural and Biochemical Characterization of Apicomplexan Inorganic Pyrophosphatases
title_full_unstemmed	Structural and Biochemical Characterization of Apicomplexan Inorganic Pyrophosphatases
title_sort	structural and biochemical characterization of apicomplexan inorganic pyrophosphatases
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/4628c75d182f4e7996d49b30de5f982a
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Structural and Biochemical Characterization of Apicomplexan Inorganic Pyrophosphatases

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