User:Madeleine Wilson/Sandbox 1
From Proteopedia
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[[Image:AdoHcy.jpg|200px|right|thumb|S-adenosyl homocysteine (SAH)]] | [[Image:AdoHcy.jpg|200px|right|thumb|S-adenosyl homocysteine (SAH)]] | ||
The reaction is catalyzed by Y305, Y245, carbonyl oxygens of the main chain in residues 295 and 290. Y305 and the carbonyl oxygens stabilize and pull electron density off a water to pull on one of the hydrogens off the nitrogen of the lysine, while oxygen of Y245 pulls on the other hydrogen of the nitrogen. Both of these actions allow nitrogen to become more nucleophilic and attack the carbon of the methyl group on the SAM, which is attached to a positively charged sulfur. The methyl group is then transferred and the sulfur is neutral; SAM has been converted to S-adenosyl homocysteine (SAH). <ref name="Xiao" /> | The reaction is catalyzed by Y305, Y245, carbonyl oxygens of the main chain in residues 295 and 290. Y305 and the carbonyl oxygens stabilize and pull electron density off a water to pull on one of the hydrogens off the nitrogen of the lysine, while oxygen of Y245 pulls on the other hydrogen of the nitrogen. Both of these actions allow nitrogen to become more nucleophilic and attack the carbon of the methyl group on the SAM, which is attached to a positively charged sulfur. The methyl group is then transferred and the sulfur is neutral; SAM has been converted to S-adenosyl homocysteine (SAH). <ref name="Xiao" /> | ||
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==Inhibitors== | ==Inhibitors== | ||
[[Image:Sinefugin.jpg|200px|left|thumb|Sinegungin]] | [[Image:Sinefugin.jpg|200px|left|thumb|Sinegungin]] | ||
| - | Sinefungin is a potent methyltransferase inhibitor. It is a structural analog of S-adenosylmethionine that is more stable due to the ability to create two additional hydrogen bonds to its amine group in the active site. It has been used experimentally to inhibit the SET 7/9 protein on peritoneal fibrosis in mice and in human peritoneal mesothelial cells. Tamura et al. (2018) found that sinefungin suppressed the cell accumulation and thickening in methylglyoxal peritoneal fibrosis. | + | Sinefungin is a potent methyltransferase inhibitor. It is a structural analog of S-adenosylmethionine that is more stable due to the ability to create two additional hydrogen bonds to its amine group in the active site. It has been used experimentally to inhibit the SET 7/9 protein on peritoneal fibrosis in mice and in human peritoneal mesothelial cells. <ref name="Schluck">PMID: 8995524</ref> Tamura et al. (2018) found that sinefungin suppressed the cell accumulation and thickening in methylglyoxal peritoneal fibrosis. <ref name="Tamura">PMID: 29723250</ref> |
</StructureSection> | </StructureSection> | ||
Revision as of 01:44, 10 April 2019
Lysine Methyl Transferase, Homo Sapiens
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References
- ↑ DesJarlais R, Tummino PJ. Role of Histone-Modifying Enzymes and Their Complexes in Regulation of Chromatin Biology. Biochemistry. 2016 Mar 22;55(11):1584-99. doi: 10.1021/acs.biochem.5b01210. Epub , 2016 Jan 26. PMID:26745824 doi:http://dx.doi.org/10.1021/acs.biochem.5b01210
- ↑ 2.0 2.1 doi: https://dx.doi.org/10.1016/j.apsb.2013.04.007
- ↑ 3.0 3.1 Dong X, Weng Z. The correlation between histone modifications and gene expression. Epigenomics. 2013 Apr;5(2):113-6. doi: 10.2217/epi.13.13. PMID:23566087 doi:http://dx.doi.org/10.2217/epi.13.13
- ↑ 4.0 4.1 Xiao B, Jing C, Wilson JR, Walker PA, Vasisht N, Kelly G, Howell S, Taylor IA, Blackburn GM, Gamblin SJ. Structure and catalytic mechanism of the human histone methyltransferase SET7/9. Nature. 2003 Feb 6;421(6923):652-6. Epub 2003 Jan 22. PMID:12540855 doi:10.1038/nature01378
- ↑ Del Rizzo PA, Trievel RC. Substrate and product specificities of SET domain methyltransferases. Epigenetics. 2011 Sep 1;6(9):1059-67. doi: 10.4161/epi.6.9.16069. Epub 2011 Sep, 1. PMID:21847010 doi:http://dx.doi.org/10.4161/epi.6.9.16069
- ↑ Tamura R, Doi S, Nakashima A, Sasaki K, Maeda K, Ueno T, Masaki T. Inhibition of the H3K4 methyltransferase SET7/9 ameliorates peritoneal fibrosis. PLoS One. 2018 May 3;13(5):e0196844. doi: 10.1371/journal.pone.0196844., eCollection 2018. PMID:29723250 doi:http://dx.doi.org/10.1371/journal.pone.0196844
7. Tamura, R., Doi, S., Nakashima, A., Sasaki, K., Maeda, K., Ueno, T., & Masaki, T. (2018). Inhibition of the H3K4 methyltransferase SET7/9 ameliorates peritoneal fibrosis. PloS one, 13(5), e0196844. doi:10.1371/journal.pone.0196844
8. Schluckebier et al. (1997), Differential binding of S-andeosylmethionine S-adenosylhomocysteine and Sinefungin to adenine-specific DNA methyltransferase M. TaqI; J. Mol. Biol., 265 56
