Analysis of JmjC Demethylase-Catalyzed Demethylation Using Geometrically-Constrained Lysine Analogues
The dynamic post-translational modifications of histones play important roles in the regulation of transcription in animals. The demethylation of N(ε)-methyl lysine residues in the N-terminal tail of histone H3 is catalyzed by demethylases, of which the largest family is the ferrous iron and 2-oxogl...
| मुख्य लेखकों: | , , , , , |
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| स्वरूप: | Journal article |
| भाषा: | English |
| प्रकाशित: |
American Chemical Society
2015
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| _version_ | 1826269727444434944 |
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| author | Langley, G Brinkø, A Münzel, M Walport, L Schofield, C Hopkinson, R |
| author_facet | Langley, G Brinkø, A Münzel, M Walport, L Schofield, C Hopkinson, R |
| author_sort | Langley, G |
| collection | OXFORD |
| description | The dynamic post-translational modifications of histones play important roles in the regulation of transcription in animals. The demethylation of N(ε)-methyl lysine residues in the N-terminal tail of histone H3 is catalyzed by demethylases, of which the largest family is the ferrous iron and 2-oxoglutarate dependent demethylases (JmjC KDMs), which catalyze demethylation via initial hydroxylation of the N-methyl groups. We report studies on the conformational requirements of the JmjC KDM substrates using N-methylated lysine analogues prepared by metathesis reactions of suitably protected N-allylglycine. The results support the proposed requirement for a positively charged N(ε)-amino group in JmjC KDM catalysis. Demethylation of a trans-C-4/C-5 dehydrolysine substrate analogue was observed with representative KDM4 subfamily members KDM4A, KDM4B and KDM4E, and KDM7B, which are predicted, based on crystallographic analyses, to bind the N(ε)-methylated lysine residue in different conformations during catalysis. This information may be useful in the design of JmjC KDM selective inhibitors. |
| first_indexed | 2024-03-06T21:29:37Z |
| format | Journal article |
| id | oxford-uuid:443e77bb-ab24-4fd3-be98-fb6aa1a1b8b9 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:29:37Z |
| publishDate | 2015 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | oxford-uuid:443e77bb-ab24-4fd3-be98-fb6aa1a1b8b92022-03-26T15:00:24ZAnalysis of JmjC Demethylase-Catalyzed Demethylation Using Geometrically-Constrained Lysine AnaloguesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:443e77bb-ab24-4fd3-be98-fb6aa1a1b8b9EnglishSymplectic Elements at OxfordAmerican Chemical Society2015Langley, GBrinkø, AMünzel, MWalport, LSchofield, CHopkinson, RThe dynamic post-translational modifications of histones play important roles in the regulation of transcription in animals. The demethylation of N(ε)-methyl lysine residues in the N-terminal tail of histone H3 is catalyzed by demethylases, of which the largest family is the ferrous iron and 2-oxoglutarate dependent demethylases (JmjC KDMs), which catalyze demethylation via initial hydroxylation of the N-methyl groups. We report studies on the conformational requirements of the JmjC KDM substrates using N-methylated lysine analogues prepared by metathesis reactions of suitably protected N-allylglycine. The results support the proposed requirement for a positively charged N(ε)-amino group in JmjC KDM catalysis. Demethylation of a trans-C-4/C-5 dehydrolysine substrate analogue was observed with representative KDM4 subfamily members KDM4A, KDM4B and KDM4E, and KDM7B, which are predicted, based on crystallographic analyses, to bind the N(ε)-methylated lysine residue in different conformations during catalysis. This information may be useful in the design of JmjC KDM selective inhibitors. |
| spellingShingle | Langley, G Brinkø, A Münzel, M Walport, L Schofield, C Hopkinson, R Analysis of JmjC Demethylase-Catalyzed Demethylation Using Geometrically-Constrained Lysine Analogues |
| title | Analysis of JmjC Demethylase-Catalyzed Demethylation Using Geometrically-Constrained Lysine Analogues |
| title_full | Analysis of JmjC Demethylase-Catalyzed Demethylation Using Geometrically-Constrained Lysine Analogues |
| title_fullStr | Analysis of JmjC Demethylase-Catalyzed Demethylation Using Geometrically-Constrained Lysine Analogues |
| title_full_unstemmed | Analysis of JmjC Demethylase-Catalyzed Demethylation Using Geometrically-Constrained Lysine Analogues |
| title_short | Analysis of JmjC Demethylase-Catalyzed Demethylation Using Geometrically-Constrained Lysine Analogues |
| title_sort | analysis of jmjc demethylase catalyzed demethylation using geometrically constrained lysine analogues |
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