Methylation, of proteins

A high intracerebral level of S-adenosylhomocysteine may inhibit methylation reactions involving S-adenosyl-methionine. The metabolic repercussions would be extensive, including deficient methylation of proteins and of phos-phatidylethanolamine as well as an inhibition of catechol-O-methyltransferase and histamine-N-methyltransferase. 

N-terminal methylation of proteins is possible and can play a major role in mitosis. Chen etal. discovered that the N-terminal serine or proline of regulator of chromatin condensation 1 (RCCl) is methylated. RCCl associates with chromatin, binding to histones H2 A and H2B, regulated by Ran, a GTPase. " For methylation to occur, the initiating methionine must be removed and a proline and lysine must be at positions 3 and 4, respectively. If RCCl is N-terminal methylation deficient, its binding to histones loses efficiency, which can cause spindle pole defects and ultimately cause problems in cell division. This work suggests the first known function for N-terminal protein methylation. ... 

Polevoda, B. and Sherman, F. (2007) Methylation of proteins involved in translation. Molecular Microbiology, 65 (3), 590-606. 

Methylation of proteins and lipids has been observed in the tissues of several species, including humans, after exposure via inhalation. Methylated DNA bases have also been detected following exposure of rodents in vivo or rodent cells in vitro to methyl bromide. 

Zhou XW, Gustafsson JA, Tanila H, Bjorkdahl C, Liu R, Winblad B, Pei JJ (2008a) Tau hyperphosphorylation correlates with reduced methylation of protein phosphatase 2A. Neutobiol Dis 31(3) 386-394... 

Stock, A., Clarke, S., Clarke, C., Stock, J. (1987). N-terminal methylation of proteins structure, function and specificity. FEBS Lett. 220, 8-14. 

Protein Methylases. Because of the work of Paik and Kim primarily, much is known about the enzymes involved in the methylation of proteins. They have isolated three protein methylases to various stages of purity and have shown that each has unique specificity properties. All of the protein methylases studied require S-adenosyl-L-methionine as co-factor, although there have been reports of methionine serving as the methyl donor (200,201). 

Biomethylation (enzymatic transmethylation) occurs in all living cells, and is an essential part of cellular metabolism, leading to methylation of proteins, nucleic acid bases, polysaccharides, and fatty acids. However, not all... 

The reader may find of interest the following papers on methylation of proteins which do not come within the scope of this review (102, 76, 134-136). 

This experiment provides a nice example of the application of spectroscopy to biochemistry. After presenting the basic theory for the spectroscopic treatment of protein-ligand interactions, a procedure for characterizing the binding of methyl orange to bovine serum albumin is described. 

While electrospray is used for molecules of all molecular masses, it has had an especially marked impact on the measurement of accurate molecular mass for proteins. Traditionally, direct measurement of molecular mass on proteins has been difficult, with the obtained values accurate to only tens or even hundreds of Daltons. The advent of electrospray means that molecular masses of 20,000 Da and more can be measured with unprecedented accuracy (Figure 40.6). This level of accuracy means that it is also possible to identify post-translational modifications of proteins (e.g., glycosylation, acetylation, methylation, hydroxylation, etc.) and to detect mass changes associated with substitution or deletion of a single amino acid. 

Hydroxylated amino acids (eg, 4-hydroxyproline, 5-hydroxylysine) and A/-methylated amino acids (eg, /V-methylhistidine) are obtained by the acid hydrolysis of proteins. y-Carboxyglutamic acid occurs as a component of some sections of protein molecules it decarboxylates spontaneously to L-glutamate at low pH. These examples are formed upon the nontranslational modification of protein and are often called secondary protein amino acids... 

FIGURE 9.19 Proteins containing the C-terminal sequence CAAX can undergo prenylation reactions that place thioether-linked farnesyl or geranylgeranyl groups at the cysteine side chain. Prenylation is accompanied by removal of the AAX peptide and methylation of the carboxyl group of the cysteine residue, which has become the C-terminal residue. 

Ribosomal RNAs characteristically contain a number of specially modified nucleotides, including pseudouridine residues, ribothymidylic acid, and methylated bases (Figure 11.26). The central role of ribosomes in the biosynthesis of proteins is treated in detail in Chapter 33. Here we briefly note the significant point that genetic information in the nucleotide sequence of an mRNA is translated into the amino acid sequence of a polypeptide chain by ribosomes. 

Transfer RNA (tRNA) serves as a carrier of amino acid residues for protein synthesis. Transfer RNA molecules also fold into a characteristic secondary structure (marginal figure). The amino acid is attached as an aminoacyl ester to the 3 -terminus of the tRNA. Aminoacyl-tRNAs are the substrates for protein biosynthesis. The tRNAs are the smallest RNAs (size range—23 to 30 kD) and contain 73 to 94 residues, a substantial number of which are methylated or otherwise unusually modified. Transfer RNA derives its name from its role as the carrier of amino acids during the process of protein synthesis (see Chapters 32 and 33). Each of the 20 amino acids of proteins has at least one unique tRNA species dedicated to chauffeuring its delivery to ribosomes for insertion into growing polypeptide chains, and some amino acids are served by several tRNAs. For example, five different tRNAs act in the transfer of leucine into... 

Carboline derivatives in various oxidation states have been isolated from a number of natural sources as artifacts. )3-Carboline has been obtained from charred insects, j8-carboline and l-methyl-)3-carboline have been found in cigarette smoke,and the formation of tetrahydro-j8-carboline derivatives has been shown to be responsible for the destruction of tryptophan in acid hydrolyzates of proteins. The golden-yeUow fluorescence observed when enterochromaffin cells are flxed in formaldehyde has been related to their content of... 

Dacarbazine is activated by photodecomposition (chemical breakdown caused by radiant energy) and by enzymatic N-demethylation. Formation of a methyl carbonium ion results in methylation of DNA and RNA and inhibition of nucleic acid and protein synthesis. Cells in all phases of the cell cycle are susceptible to dacarbazine. The drug is not appreciably protein bound, and it does not enter the central nervous system. 

Evolution has provided the cell with a repertoire of 20 amino acids to build proteins. The diversity of amino acid side chain properties is enormous, yet many additional functional groups have been selectively chosen to be covalently attached to side chains and this further increases the unique properties of proteins. Diese additional groups play a regulatory role allowing the cell to respond to changing cellular conditions and events. Known covalent modifications of proteins now include phosphorylation, methylation, acetylation, ubi-quitylation, hydroxylation, uridylylation and glycosyl-ation, among many others. Intense study in this field has shown the addition of a phosphate moiety to a protein... 

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