Methylation arginine

P RMTs lead to the methylation of certain arginine residues in histones as depicted in Table 12.1. They are not restricted to histone substrates but also catalyze the methylation of other proteins that play a role in signal transduction and cell proliferation [15]. Usually glycine-alanine-arginine patches (called GAR motifs) 

Enzyme Links to disease (examples) Major target site(s)° 

PRMTl Coactivator of hormone H4R3, NAB2p, NPL3p, 

PRMT2 Coactivator for the androgen receptor [57] Catalytically inactive 

PRMT4 (CARMl) Involved in estrogen-driven H3R2, H3R17, H3R26 

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L-NAME (N-nitro-L-arginine methyl ester), like L-NMMA, is a structural analogue of L-arginine and competes with L-arginine for NO-synthase, which uses L-arginine as a substrate for the formation of NO. L-NMMA and L-NAME are very effective NO-synthesis inhibitors, both in vitro and in vivo. 

C7H(iN204 616-79-5) see Afloqualone nitro-L-arginine methyl ester hydrochloride (C7H ftCIN,04 51298-62-5) see Angiotensinamide... 

N-Nitro-L-arginine methyl ester (L-NAME) is an inhibitor of NOS L-NAME reportedly reduces the volume of cortical and striatal infarct after middle cerebral artery occlusion in the rat. This protection can be reversed by co-injection of L-arginine. L-NAME also reduced the excitotoxic damage induced by NMDA injection. Finally, the authors showed that L-NAME reduced glutamate efflux produced by ischaemic injury in rats. The authors concluded that NOS induced by NMDA receptor overstimulation is a key event in the neuronal injury cascade (Buisson eta/., 1993). 

NO is a gaseous neurotransmitter implicated in signaling in the central and peripheral nervous system as well as in the immune system and the vasculature. NO is formed from L-arginine by nitric oxide synthase (NOS). There are three isoforms of NOS. All isoforms require NADPH as a cofactor, use L-arginine as a substrate, and are inhibited by Nw-nitro-L-arginine methyl ester (L-NAME). The three isoforms are separate gene products. One isoform of NOS is a cytosolic, calcium/calmodulin-independent, inducible enzyme (iNOS). It is found in macrophages, neutrophils, vascular smooth muscle, and endothelia. The iNOS... 

The accumulation of inflammatory cells (leukocytes and macrophages) in the arterial wall is another inducer of hypertension. For example, it has been shown that NO blockade in the aortas in L-Nitro arginine methyl ester(NAME)-treated rats resulted in the accumulation... 

Abbreviations BSO, D.L-buthionine-. i -sulfoxime L , lipid alkyl radicals LH, lipid LO, Upid alkoxyl radicals LOO, Upid peroxyl radicals L-NAME, yV -nitro-L-arginine-methyl ester MBl, methylene bridge index (mean number of h -aUytic methylene positions per fatty add) NO, nitric oxide NOS, nitric oxide synthase NO, nitrite N02, nitrogen dioxide NO2CI, nitryl chloride O2 , superoxide OH, hydroxyl radical OL, epoxyaUyhc radical OLOO, epoxyperoxyl radical 0=NOO , peroxynitrite SNAP, S-nitroso-iV-acetyl-D.L-penicillamine SOD, superoxide dismutase contd. onp. 98, Subcellular Biochemistry, Volume 36 Phospholipid Metabolism in Apoptosis. 

Schafer DA, Schroer TA (1999) Actin-related proteins. Annu Rev Cell Dev Biol 15 341-363 Schurter BT, Koh SS, Chen D, Bunick GJ, Harp JM, Hanson BL, Henschen-Edman A, Mackay DR, Stallcup MR, Aswad DW (2001) Methylation of histone H3 by coactivator-associated arginine methyl-transferase 1. Biochemistry 40 5747—5756... 

Bedford MT, Richard S (2005) Arginine methylation an emerging regulator of protein function. Mol Cell 18(3) 263-272... 

Chevillard-Briet M, Trouche D, Vandel L (2002) Control of CBP co-activating activity by arginine methylation. EMBO J 21 5457-5466... 

Cuthbert GL, Daujat S, Snowden AW, Erdjument-Bromage H, Hagiwara T, Yamada M, Schneider R, Gregory PD, Tempst P, Bannister AJ, Kouzarides T (2004) Histone deimination antagonizes arginine methylation. Cell 118 545-553... 

Bedalov A, Gatbonton T, Irvine WP, Gottschling DE, Simon JA (2001) Identification of a small molecule inhibitor of Sir2p. Proc Natl Acad Sci USA 98(26) 15113-15118 Bedford MT, Richard S (2005) Arginine methylation an emerging regulator of protein function. Mol Cell 18 263-272... 

Wang Y, Wysocka J, Sayegh J, Lee YH, Perlin JR, Leonelli L, Sonbuchner LS, McDonald CH, Cook RG, Dou Y, Roeder RG, Clarke S, Stall cup MR, Allis CD, Coonrod S A (2004) Human PAD4 regulates histone arginine methylation levels via demethylimination. Science 306(5694) 279-283... 

Wang, Y. et al. (2004) Human PAD4 regulates histone arginine methylation levels via demethylimination. Science, 306, 279-283. 

Thompson, P.R. and Fast, W. (2006) Histone citrullination by protein arginine deiminase is arginine methylation a green light or a roadblock ACS Chemical Biology, 1, 433-441. 

Kirmizis, A. et al. (2007) Arginine methylation at histone H3R2 controls deposition of H3K4 trimethylation. Nature, 449, 928-932. 

Pahlich, S., Zakaryan, R.P. and Gehring, H. (2006) Protein arginine methylation Cellular functions and methods of analysis. Biochimica et Biophysica Acta, 1764 (12), 1890-1903. 

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