Crystal structure of the PHF8 Jumonji domain, an Nepsilon-methyl lysine demethylase.
Crystallographic analysis of the catalytic domain of PHD finger protein 8 (PHF8), an N(epsilon)-methyl lysine histone demethylase associated with mental retardation and cleft lip/palate, reveals a double-stranded beta-helix fold with conserved Fe(II) and cosubstrate binding sites typical of the 2-ox...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2010
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| _version_ | 1826277753096241152 |
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| author | Yue, W Hozjan, V Ge, W Loenarz, C Cooper, C Schofield, C Kavanagh, K Oppermann, U McDonough, M |
| author_facet | Yue, W Hozjan, V Ge, W Loenarz, C Cooper, C Schofield, C Kavanagh, K Oppermann, U McDonough, M |
| author_sort | Yue, W |
| collection | OXFORD |
| description | Crystallographic analysis of the catalytic domain of PHD finger protein 8 (PHF8), an N(epsilon)-methyl lysine histone demethylase associated with mental retardation and cleft lip/palate, reveals a double-stranded beta-helix fold with conserved Fe(II) and cosubstrate binding sites typical of the 2-oxoglutarate dependent oxygenases. The PHF8 active site is highly conserved with those of the FBXL10/11demethylases, which are also selective for the di-/mono-methylated lysine states, but differs from that of the JMJD2 demethylases which are selective for tri-/di-methylated states. The results rationalize the lack of activity for the clinically observed F279S PHF8 variant and they will help to identify inhibitors selective for specific N(epsilon)-methyl lysine demethylase subfamilies. |
| first_indexed | 2024-03-06T23:33:39Z |
| format | Journal article |
| id | oxford-uuid:6ce5a722-3c8a-483f-9153-239c875353fd |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:33:39Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:6ce5a722-3c8a-483f-9153-239c875353fd2022-03-26T19:14:14ZCrystal structure of the PHF8 Jumonji domain, an Nepsilon-methyl lysine demethylase.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6ce5a722-3c8a-483f-9153-239c875353fdEnglishSymplectic Elements at Oxford2010Yue, WHozjan, VGe, WLoenarz, CCooper, CSchofield, CKavanagh, KOppermann, UMcDonough, MCrystallographic analysis of the catalytic domain of PHD finger protein 8 (PHF8), an N(epsilon)-methyl lysine histone demethylase associated with mental retardation and cleft lip/palate, reveals a double-stranded beta-helix fold with conserved Fe(II) and cosubstrate binding sites typical of the 2-oxoglutarate dependent oxygenases. The PHF8 active site is highly conserved with those of the FBXL10/11demethylases, which are also selective for the di-/mono-methylated lysine states, but differs from that of the JMJD2 demethylases which are selective for tri-/di-methylated states. The results rationalize the lack of activity for the clinically observed F279S PHF8 variant and they will help to identify inhibitors selective for specific N(epsilon)-methyl lysine demethylase subfamilies. |
| spellingShingle | Yue, W Hozjan, V Ge, W Loenarz, C Cooper, C Schofield, C Kavanagh, K Oppermann, U McDonough, M Crystal structure of the PHF8 Jumonji domain, an Nepsilon-methyl lysine demethylase. |
| title | Crystal structure of the PHF8 Jumonji domain, an Nepsilon-methyl lysine demethylase. |
| title_full | Crystal structure of the PHF8 Jumonji domain, an Nepsilon-methyl lysine demethylase. |
| title_fullStr | Crystal structure of the PHF8 Jumonji domain, an Nepsilon-methyl lysine demethylase. |
| title_full_unstemmed | Crystal structure of the PHF8 Jumonji domain, an Nepsilon-methyl lysine demethylase. |
| title_short | Crystal structure of the PHF8 Jumonji domain, an Nepsilon-methyl lysine demethylase. |
| title_sort | crystal structure of the phf8 jumonji domain an nepsilon methyl lysine demethylase |
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