Methyltransferase types

Originally isolated and characterized from the petals of Clarkia breweri, salicylic acid carboxyl methyltransferase (SAMT), converts salicylic acid to methylsalicylate.14 Methysalicylate, a volatile ester, has a characteristic wintergreen scent Apart from its putative role in defense, methylsalicylate is an important chemoattractant for moth-pollinated flowers and one of the main volatiles released from Clarkia breweri flowers.44,55 SAMT is a member of the type 3 family of plant MTs. Similarly to the previously discussed families of methyltransferases, type 3 MTs are homodimeric proteins. 

Holmberg, N., Harker, M., Gibbard, C.L., Wallace, A.D., Clayton, J.C., Rawlins, S., Hellyer, A. and Safford, R. (2002) Sterol C-24 methyltransferase type 1 controls the flux of carbon into sterol biosynthesis in tobacco seed. Plant Phi/sioL, 130,303-11. 

Uroporphyrinogen I (16c), a constitutional isomer of uroporphyrinogen III, also plays no direct role in porphyrin and corrin biosynthesis, but this unnatural substrate is methylated to give 17c10c f in the presence of SAM by the methyl transferase of some bacteria. A constitutional type I dihydroisobacteriochlorin can be obtained by methylation of uroporphyrinogen I with methylase Ml. Methyltransferase M1 is able to methylate the unnatural precorrin once more to give the trimethylpyrrocorphin type I.IOc 1... 

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). 

Two additional types of methyltransferase domains have been identified in NRPSs. Yersiniabactin synthetase contains a carbon-MT domain within a Cy-MT-PCP-TE module. This domain methylates at the a-carbon of an intermediate thiazoline ring. The melithiazol synthetase utilizes an MT domain in trans to form a methyl ester at the C-terminus of the natural product. Recent in silica analysis of MT domains from secondary metabolite biosynthetic pathways has revealed the boundaries of these domains and suggests that they are typically approximately 200 amino acids in length, much shorter than previously thought. The results of this study by Mohanty and coworkers allow for the accurate prediction of N-, C-, or 0-MT activity through sequence analysis. " ... 

In vitro studies with unmodified and modified N-terminal peptides of H3 demonstrated that Lys-14 acetylation did not interfere with methylation at Lys-9 by Suv39hl, while phosphorylation at Ser-10 and acetylation at Lys-9 did (Fig. 7). Further dimethylation of Lys-9 reduced enzymatic activity [186], A Suv39h double null primary mouse embryonic fibroblasts had higher levels of Ser-10 phos-phorylated H3 than wild type cells. These mutant cells had increased numbers of micro- and polynuclei. Oversized nuclei were characteristic of subpopulation of cells. The level of Lys-9 methylated FI3 in wild type cells and Suv39h double null cells was similar, demonstrating that other FI3 methyltransferases were involved [195]. Phosphorylation of Ser-10 by Ipll/aurora was also studied. Acetylation at Lys-14 promoted the activity of the mitotic kinase, while dimethylation, but not acetylation at Lys-9, reduced activity of the kinase [186]. 

So far the major application of IVC has been to select enzymes. Griffiths has used IVC to select DNA methyltransferases and has successfully generated variants that can efficiently modify novel DNA target sequences [38]. This study provides a rare example of a laboratory-produced enzyme with a catalytic efficiency that surpasses that of the wild-type enzyme with the principle substrate. IVC has also... 

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