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...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2017-07-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-05234-y |
| _version_ | 1819042284314820608 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-21T09:38:26Z |
| format | Article |
| id | doaj.art-4628c75d182f4e7996d49b30de5f982a |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-21T09:38:26Z |
| publishDate | 2017-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-4628c75d182f4e7996d49b30de5f982a2022-12-21T19:08:33ZengNature PortfolioScientific Reports2045-23222017-07-017111410.1038/s41598-017-05234-yStructural and Biochemical Characterization of Apicomplexan Inorganic PyrophosphatasesAbhishek Jamwal0Manickam Yogavel1Malik. Z. Abdin2Swatantra. K. Jain3Amit Sharma4Molecular Medicine Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali MargMolecular Medicine Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali MargDepartment of Biotechnology, Jamia HamdardDepartment of Biotechnology, Jamia HamdardMolecular Medicine Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali MargAbstract 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.https://doi.org/10.1038/s41598-017-05234-y |
| spellingShingle | Abhishek Jamwal Manickam Yogavel Malik. Z. Abdin Swatantra. K. Jain Amit Sharma Structural and Biochemical Characterization of Apicomplexan Inorganic Pyrophosphatases Scientific Reports |
| title | 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_short | Structural and Biochemical Characterization of Apicomplexan Inorganic Pyrophosphatases |
| title_sort | structural and biochemical characterization of apicomplexan inorganic pyrophosphatases |
| url | https://doi.org/10.1038/s41598-017-05234-y |
| work_keys_str_mv | AT abhishekjamwal structuralandbiochemicalcharacterizationofapicomplexaninorganicpyrophosphatases AT manickamyogavel structuralandbiochemicalcharacterizationofapicomplexaninorganicpyrophosphatases AT malikzabdin structuralandbiochemicalcharacterizationofapicomplexaninorganicpyrophosphatases AT swatantrakjain structuralandbiochemicalcharacterizationofapicomplexaninorganicpyrophosphatases AT amitsharma structuralandbiochemicalcharacterizationofapicomplexaninorganicpyrophosphatases |