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Lysine methyltransferase

With the characterized mechanism, the next key question is the origin of its catalytic power. A prerequisite for this investigation is to reliably compute free energy barriers for both enzyme and solution reactions. By employing on-the-fly Born-Oppenheimer molecular dynamics simulations with the ab initio QM/MM approach and the umbrella sampling method, we have determined free energy profiles for the methyl-transfer reaction catalyzed by the histone lysine methyltransferase SET7/9... [Pg.346]

Wang S, Hu P, Zhang Y (2007) Ab initio quantum mechanical/molecular mechanical molecular dynamics simulation of enzyme catalysis the case of histone lysine methyltransferase set7/9. J Phys Chem B ASAP... [Pg.350]

Schneider R, Bannister AJ, Kouzarides T (2002) Unsafe sets histone lysine methyltransferases and cancer. Trends Biochem Sci 27 396-402... [Pg.350]

Yeates TO (2002) Structures of set domain proteins protein lysine methyltransferases make their mark. Cell 111 5-7... [Pg.350]

Figure 1 Covalent modifications of DNA and histones play a fundamental role in the regulation of differentiation and development. The writers, readers, and erasers of this dynamic code are potentially amenable to modulation with small molecules. Lysine methylation is a critical posttranslational modification influencing chromatin function (PMT = protein lysine methyltransferase, royal family proteins bind KMe, KDM = lysine demethylase). Figure 1 Covalent modifications of DNA and histones play a fundamental role in the regulation of differentiation and development. The writers, readers, and erasers of this dynamic code are potentially amenable to modulation with small molecules. Lysine methylation is a critical posttranslational modification influencing chromatin function (PMT = protein lysine methyltransferase, royal family proteins bind KMe, KDM = lysine demethylase).
Figure 2 Selected human protein lysine methyltransferases and their target sites on histones [11]. Figure 2 Selected human protein lysine methyltransferases and their target sites on histones [11].
Abstract First Wstone lysine methyltransferase (HLMTase) was discovered in 2000. Since then,... [Pg.337]

Dodge JE, Kang YK, Beppu H, Lei H, Li E (2004) Histone H3-K9 methyltransferase ESET is essential for early development. Mol Cell Biol 24 2478—2486 Duan Z, Zarebski A, Montoya-Durango D, Grimes HL, Horwitz M (2005) Gfil coordinates epigenetic repression of p21Cip/WAFl by recruitment of histone lysine methyltransferase G9a and histone deacetylase 1. Mol Cell Biol 280 13928-13935... [Pg.347]

There is a school of thought, which believes that HMTases are tumor suppressors especially the lysine methyltransferases because of the loss of SET domain proteins in tumor conditions, exceptions do exist like Ezh2. The well-known example of the above is RIZl, which interacts with Rb protein (again the same tumor suppressor). RIZ-1 is in chromosome lp36 region, which is commonly deleted, in more than a dozen different types of human cancers. Riz-1 expression is commonly silenced in many tumors including breast cancer, liver cancer, colon cancer, neuroblastoma, melanoma, lung cancer and osteosarcoma (Kim et al, 2003). [Pg.408]

Lysine methyltransferases have a well-established role in cancer whereas the arginine methyltransferases role is relatively less explored. Inspite of that there... [Pg.408]

Histone-lysine methyltransferases are chromatin-bound enzymes that catalyses the addition of methyl groups onto lysine or arginine residues of chromatin-bound H3 and H4 [151]. The methyl group is transferred enzymatically to the histone with S-adenosyl methionine as the methyl donor. Histone methylases have been isolated from HeLa S-3 cells [182], chick embryo nuclei [183], and rat brain chromatin [184]. The histone methyltransferases methylated H3 and H4 in nucleosomes [184]. Histone-lysine methyltransferase is a chromatin-bound enzyme [129,151]. Initial characterization of the Tetrahymena macronuclear H3 methyltransferase suggests that the enzyme has a molecular mass of 400 kDa. The enzyme preferred free histones rather than nucleosomes as substrate [138]. More recent studies have now... [Pg.221]

Qian, C. and Zhou, M.M. (2006) SET domain protein lysine methyltransferases Structure, specificity and catalysis. Cellular and Molecular Life Sciences, 63 (23), 2755-2763. [Pg.53]

Dillon, S.C., Zhang, X., Trievel, R.C. and Cheng, X. (2005) The SFT-domain protein superfamily protein lysine methyltransferases. Genome Biol(, 6 (8), 111. [Pg.53]

Histone methylation by methyltransferases is another vddely described modification that also plays an important role in regulation of transcriptional activity. Methylation can occur either on arginine or on lysine residues in the N-termini of histones and therefore this group of enzymes can be separated into protein arginine methyltransferases (PRMTs) and lysine methyltransferases (KMTs). [Pg.110]

Lysine methyltransferases catalyze the transfer of methyl groups from the cosubstrate SAM to certain lysine residues in histone proteins. To characterize modulators of these transferases, the above-mentioned antibody-based assay protocols are also applicable. [Pg.110]

Histone methylation participates in the regulation of gene expression patterns. Unlike histone acetylation, histone methylation does not alter the charge of the amino acid and hence the histone tail. There are changes in the basicity and the hydrophobicity which are relatively small when viewed at the scale of the histone but still influence the affinity of the histone tails to certain proteins, for example transcription factors, which in turn result in certain signaling events. The histone methyltransferases are usually subdivided into three classes SET domain lysine methyltransfeases, nonSET domain lysine methyltransferases and arginine methyltransferases (PRMTs). All of them utilize S-adenosylmethionine (SAM) as cosubstrate for the methylation reaction... [Pg.251]

So far nine arginine methyltransferases [46] and more than 20 lysine methyltransferases [11] have been identified in humans. Many of them show links to cancer. We discuss several of these subtypes below and an overview can be found in Tables 12.1 and 12.2. For lysine methyltransferases traditionally individual names have been used for the various subtypes. Lately, a common nomenclature for chromatin modifying enzymes has been proposed. For the human lysine methyltransferases the name KMTs should be used in analogy to (P)RMTs and eight groups (KMTl-8) with different subtypes suggested for some members [47]. But this nomenclature is not used consistently even throughout the recent literature so we provide both names if available in Table 12.2. [Pg.254]

Table 12.2 Selected lysine methyltransferases and links to cancer. Table 12.2 Selected lysine methyltransferases and links to cancer.
Lysine methyltransferases have been linked in various cases to the pathogenesis of cancer. Examples can be found for KMTs that induce repressive marks as well as for those that lead to an activating methylation pattern. Possible reasons for a disturbed regulation of methylation may result in mutations of enzymes or overexpression in cancer cells. An indication for a therapeutic benefit of potential inhibitors is often derived from siRNA knockdown of the requisite isotype. Mutations of MLLl for example are thought to be responsible for various forms of acute leukemia [63]. Overexpression of EZH2 was linked to breast or prostate cancer [64] and increased levels in human cancers have also been observed for G9a. Increased mRNA levels for... [Pg.256]

For lysine methyltransferases few specific inhibitors have been reported so far and all were discovered by random screening procedures. The first inhibitor that was... [Pg.260]

Figure 12.4 Lysine methyltransferase inhibitors (all from random screening, IC50 values and enzymes in brackets). Figure 12.4 Lysine methyltransferase inhibitors (all from random screening, IC50 values and enzymes in brackets).
The compound BIX-01294 was identified as an inhibitor of G9a in the low micromolar region and a selectivity against SUV39H1 and PRMTl was shown. BIX-01294 also showed a reduction of the methylation levels of H3K9 dimethylation. Known sites of other lysine methyltransferases like H3K27 or H4K20 were not affected. In the same study dual inhibitors of arginine and lysine methyltransferases like BIX-01338 were reported [82],... [Pg.261]

Rathert, P., Dhayalan, A., Murakami, M., Zhang, X., Tamas, R., Jurkowska, R., Komatsu, Y., Shinkai, Y, Cheng, X. and Jeltsch, A. (2008) Protein lysine methyltransferase G9a acts on non-histone targets. Nature Chemical Biology,... [Pg.262]

Aniello, F., ColeDa, G., Muscariello, G., Lanza, A., Ferrara, D., Branno, M. and Minucd, S. (2006) Expression of four histone lysine-methyltransferases in parotid gland tumors. Anticancer Research, 26, 2063-2067. [Pg.267]


See other pages where Lysine methyltransferase is mentioned: [Pg.341]    [Pg.342]    [Pg.347]    [Pg.249]    [Pg.338]    [Pg.400]    [Pg.400]    [Pg.36]    [Pg.36]    [Pg.38]    [Pg.76]    [Pg.110]    [Pg.117]    [Pg.252]    [Pg.253]    [Pg.256]    [Pg.257]    [Pg.260]   
See also in sourсe #XX -- [ Pg.249 , Pg.331 , Pg.333 ]

See also in sourсe #XX -- [ Pg.36 ]




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Histone lysine methyltransferase

Histone lysine methyltransferases

Histone lysine methyltransferases HKMTs)

Human protein lysine methyltransferases

Lysine methyltransferases

Lysine methyltransferases

Methyltransferase

Methyltransferases

Protein lysine methyltransferases

SET domain lysine methyltransferase

SET domain lysine methyltransferases

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