2v7e
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Coactivator-associated arginine methyltransferase (CARM1) is a | + | Coactivator-associated arginine methyltransferase (CARM1) is a transcriptional coactivator that methylates Arg17 and Arg26 in histone H3. CARM1 contains a conserved protein arginine methyltransferase (PRMT) catalytic core flanked by unique pre- and post-core regions. The crystal structures of the CARM1 catalytic core in the apo and holo states reveal cofactor-dependent formation of a substrate-binding groove providing a specific access channel for arginine to the active site. The groove is supported by the first eight residues of the post-core region (C-extension), not present in other PRMTs. In vitro methylation assays show that the C-extension is essential for all histone H3 methylation activity, whereas the pre-core region is required for methylation of Arg26, but not Arg17. Kinetic analysis shows Arg17 methylation is potentiated by pre-acetylation of Lys18, and this is reflected in k(cat) rather than K(m). Together with the absence of specificity subsites in the structure, this suggests an electrostatic sensing mechanism for communicating the modification status of vicinal residues as part of the syntax of the 'histone code.' |
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | Insights into histone code syntax from structural and biochemical studies of CARM1 methyltransferase., Yue WW, Hassler M, Roe SM, Thompson-Vale V, Pearl LH, EMBO J. 2007 Sep 20 | + | Insights into histone code syntax from structural and biochemical studies of CARM1 methyltransferase., Yue WW, Hassler M, Roe SM, Thompson-Vale V, Pearl LH, EMBO J. 2007 Oct 17;26(20):4402-12. Epub 2007 Sep 20. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17882261 17882261] |
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Hassler, M.]] | [[Category: Hassler, M.]] | ||
| - | [[Category: Pearl, L | + | [[Category: Pearl, L H.]] |
| - | [[Category: Roe, S | + | [[Category: Roe, S M.]] |
[[Category: Thompson-Vale, V.]] | [[Category: Thompson-Vale, V.]] | ||
| - | [[Category: Yue, W | + | [[Category: Yue, W W.]] |
[[Category: HG]] | [[Category: HG]] | ||
[[Category: alternative splicing]] | [[Category: alternative splicing]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:53:47 2008'' |
Revision as of 16:53, 21 February 2008
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CRYSTAL STRUCTURE OF COACTIVATOR-ASSOCIATED ARGININE METHYLTRANSFERASE 1 (CARM1), UNLIGANDED
Overview
Coactivator-associated arginine methyltransferase (CARM1) is a transcriptional coactivator that methylates Arg17 and Arg26 in histone H3. CARM1 contains a conserved protein arginine methyltransferase (PRMT) catalytic core flanked by unique pre- and post-core regions. The crystal structures of the CARM1 catalytic core in the apo and holo states reveal cofactor-dependent formation of a substrate-binding groove providing a specific access channel for arginine to the active site. The groove is supported by the first eight residues of the post-core region (C-extension), not present in other PRMTs. In vitro methylation assays show that the C-extension is essential for all histone H3 methylation activity, whereas the pre-core region is required for methylation of Arg26, but not Arg17. Kinetic analysis shows Arg17 methylation is potentiated by pre-acetylation of Lys18, and this is reflected in k(cat) rather than K(m). Together with the absence of specificity subsites in the structure, this suggests an electrostatic sensing mechanism for communicating the modification status of vicinal residues as part of the syntax of the 'histone code.'
About this Structure
2V7E is a Single protein structure of sequence from Mus musculus with as ligand. Known structural/functional Sites: , and . Full crystallographic information is available from OCA.
Reference
Insights into histone code syntax from structural and biochemical studies of CARM1 methyltransferase., Yue WW, Hassler M, Roe SM, Thompson-Vale V, Pearl LH, EMBO J. 2007 Oct 17;26(20):4402-12. Epub 2007 Sep 20. PMID:17882261
Page seeded by OCA on Thu Feb 21 18:53:47 2008
Categories: Mus musculus | Single protein | Hassler, M. | Pearl, L H. | Roe, S M. | Thompson-Vale, V. | Yue, W W. | HG | Alternative splicing | Arginine methyltransferase | Chromatin regulator | Co- activator | Cytoplasm | Histone modification | Methyltransferase | Nucleus | S-adenosyl-l-methionine | Transcription | Transcription regulation | Transferase
