Conservation of the unusual dimeric JmjC fold of JMJD7 from Drosophila melanogaster to humans
Abstract The JmjC family of 2-oxoglutarate dependent oxygenases catalyse a range of hydroxylation and demethylation reactions in humans and other animals. Jumonji domain-containing 7 (JMJD7) is a JmjC (3S)-lysyl-hydroxylase that catalyses the modification of Developmentally Regulated GTP Binding Pro...
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| Format: | Article |
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Nature Portfolio
2022-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-10028-y |
| _version_ | 1818022185664512000 |
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| author | Rasheduzzaman Chowdhury Martine I. Abboud James Wiley Anthony Tumber Suzana Markolovic Christopher J. Schofield |
| author_facet | Rasheduzzaman Chowdhury Martine I. Abboud James Wiley Anthony Tumber Suzana Markolovic Christopher J. Schofield |
| author_sort | Rasheduzzaman Chowdhury |
| collection | DOAJ |
| description | Abstract The JmjC family of 2-oxoglutarate dependent oxygenases catalyse a range of hydroxylation and demethylation reactions in humans and other animals. Jumonji domain-containing 7 (JMJD7) is a JmjC (3S)-lysyl-hydroxylase that catalyses the modification of Developmentally Regulated GTP Binding Proteins 1 and 2 (DRG1 and 2); JMJD7 has also been reported to have histone endopeptidase activity. Here we report biophysical and biochemical studies on JMJD7 from Drosophila melanogaster (dmJMJD7). Notably, crystallographic analyses reveal that the unusual dimerization mode of JMJD7, which involves interactions between both the N- and C-terminal regions of both dmJMJD7 monomers and disulfide formation, is conserved in human JMJD7 (hsJMJD7). The results further support the assignment of JMJD7 as a lysyl hydroxylase and will help enable the development of selective inhibitors for it and other JmjC oxygenases. |
| first_indexed | 2024-04-14T08:29:04Z |
| format | Article |
| id | doaj.art-77195d9f25814b63ac7af57680c41a8a |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-14T08:29:04Z |
| publishDate | 2022-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-77195d9f25814b63ac7af57680c41a8a2022-12-22T02:03:58ZengNature PortfolioScientific Reports2045-23222022-04-0112111010.1038/s41598-022-10028-yConservation of the unusual dimeric JmjC fold of JMJD7 from Drosophila melanogaster to humansRasheduzzaman Chowdhury0Martine I. Abboud1James Wiley2Anthony Tumber3Suzana Markolovic4Christopher J. Schofield5Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of OxfordChemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of OxfordChemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of OxfordChemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of OxfordChemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of OxfordChemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of OxfordAbstract The JmjC family of 2-oxoglutarate dependent oxygenases catalyse a range of hydroxylation and demethylation reactions in humans and other animals. Jumonji domain-containing 7 (JMJD7) is a JmjC (3S)-lysyl-hydroxylase that catalyses the modification of Developmentally Regulated GTP Binding Proteins 1 and 2 (DRG1 and 2); JMJD7 has also been reported to have histone endopeptidase activity. Here we report biophysical and biochemical studies on JMJD7 from Drosophila melanogaster (dmJMJD7). Notably, crystallographic analyses reveal that the unusual dimerization mode of JMJD7, which involves interactions between both the N- and C-terminal regions of both dmJMJD7 monomers and disulfide formation, is conserved in human JMJD7 (hsJMJD7). The results further support the assignment of JMJD7 as a lysyl hydroxylase and will help enable the development of selective inhibitors for it and other JmjC oxygenases.https://doi.org/10.1038/s41598-022-10028-y |
| spellingShingle | Rasheduzzaman Chowdhury Martine I. Abboud James Wiley Anthony Tumber Suzana Markolovic Christopher J. Schofield Conservation of the unusual dimeric JmjC fold of JMJD7 from Drosophila melanogaster to humans Scientific Reports |
| title | Conservation of the unusual dimeric JmjC fold of JMJD7 from Drosophila melanogaster to humans |
| title_full | Conservation of the unusual dimeric JmjC fold of JMJD7 from Drosophila melanogaster to humans |
| title_fullStr | Conservation of the unusual dimeric JmjC fold of JMJD7 from Drosophila melanogaster to humans |
| title_full_unstemmed | Conservation of the unusual dimeric JmjC fold of JMJD7 from Drosophila melanogaster to humans |
| title_short | Conservation of the unusual dimeric JmjC fold of JMJD7 from Drosophila melanogaster to humans |
| title_sort | conservation of the unusual dimeric jmjc fold of jmjd7 from drosophila melanogaster to humans |
| url | https://doi.org/10.1038/s41598-022-10028-y |
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