3.5.3.18 (2S)-2-amino-5-(ethanimidoylamino)pentanoic acid - 61103 3.5.3.18 (2S)-2-amino-5-(N'-butylcarbamimidamido)pentanoic acid - 59398 3.5.3.18 (2S)-2-amino-5-(pent-4-enimidoylamino)pentanoic acid - 61111 3.5.3.18 (2S)-2-amino-5-(pentanimidoylamino)pentanoic acid - 61110 3.5.3.18 (2S)-2-amino-5-(propanimidoylamino)pentanoic acid - 61104 3.5.3.18 (2S)-2-amino-5-[(4E)-hex-4-enimidoylamino]pentanoic acid - 61109 3.5.3.18 (2S)-2-amino-5-[N'-(3,3,3-trifluoropropyl)carbamimidamido]pentanoic acid - 67204 3.5.3.18 (2S)-2-amino-5-[N'-(3-methoxypropyl)carbamimidamido]pentanoic acid - 61102 3.5.3.18 (2S)-2-amino-5-[N'-(4-amino-4-oxobutyl)carbamimidamido]pentanoic acid - 67206 3.5.3.18 (2S)-2-amino-5-[N'-(but-3-en-1-yl)carbamimidamido]pentanoic acid - 61264 3.5.3.18 (2S)-2-amino-5-[N'-(but-3-yn-1-yl)carbamimidamido]pentanoic acid - 67211 3.5.3.18 (2S)-2-amino-5-[N'-(nitromethyl)carbamimidamido]pentanoic acid - 67205 3.5.3.18 (2S)-2-amino-5-[N'-(pent-4-en-1-yl)carbamimidamido]pentanoic acid - 63056 3.5.3.18 2,3-dimethoxy-1,4-naphthoquinone 1 mM 34390 3.5.3.18 2-(N,N-diethylamino)-diazenolate-2-oxide 1 mM 35231 3.5.3.18 2-(N,N-dimethylamino)-diazenolate-2-oxide S-nitrosylation of apo-enzyme, holo-enzyme resists, reaction with two of five Cys-residues 33833 3.5.3.18 2-(N,N-dimethylamino)-diazenolate-2-oxide i.e. DEANONOate, inhibition by S-nitrosylation, reversed by dithiothreitol 33833 3.5.3.18 2-(N,N-dimethylamino)diazenolate-2-oxide 1 mM, 50% inhibition of DDAH-1 26703 3.5.3.18 2-(N,N-dimethylamino)diazenolate-2-oxide 1 mM, 50% inhibition of DDAH-1; 1 mM, 50% inhibition of DDAH-1 26703 3.5.3.18 2-amino-4-(NG-methyl-guanidino)butanoic acid incubation of lysed red blood cells, dose dependent inhibition of NG,NG-dimethyl-L-arginine degradation with the highest dose (1 mM) reversing the pattern to a net increase in NG,NG-dimethyl-L-arginine concentration for the 1- and 3h time points 60963 3.5.3.18 2-amino-4-(NG-methyl-guanidino)butanoic acid a series of analogues designed, reversible DDAH inhibitors 60963 3.5.3.18 2-chloroacetamidine irreversible inhibition in a time- and concentration-dependent manner 6252 3.5.3.18 2-hydroxymethyl-4-chloropyridine solution studies support an inactivation mechanismin in which the active site Asp66 residue stabilizes the pyridinium form of the inactivator, which has enhanced reactivity toward the active site Cys, resulting in covalent bond formation, loss of the halide, and irreversible inactivation 169865 3.5.3.18 4-hydroxy-2-nonenal 50 microM, 50% relative activity 1426 3.5.3.18 4-hydroxy-nonenal dose-dependently inhibits DDAH activity with 15% inhibition at 0.01 mM and complete inhibition at 0.5 mM 37847 3.5.3.18 angiotensin II 1 microM, about 55% relative activity; 1 microM, about 55% relative activity 661 3.5.3.18 aprotinin inhibitor NG,NG-dimethyl-L-arginine release from freeze-thaw whole blood 34% inhibited 132661 3.5.3.18 Cd2+ - 52 3.5.3.18 CoCl2 - 414 3.5.3.18 Cu2+ - 19 3.5.3.18 cytokine induced nitric-oxide synthesis - 151879 3.5.3.18 D-arginine 0.1 mM D-arginine reduces DDAH activity to 24.7% 1255 3.5.3.18 darbepoetin alpha inhibits DDAH in a dose dependent manner, inhibition of DDAH is abolished by incubation with EPO antibody or with antioxidant pyrrolidine dithiocarbamate 132660 3.5.3.18 epoetin beta inhibits DDAH in a dose dependent manner, inhibition of DDAH is abolished by incubation with EPO antibody or with antioxidant pyrrolidine dithiocarbamate 132659 3.5.3.18 erythropoetin 200 units/ml, about 75% relative activity; 200 units/ml, about 75% relative activity 75598 3.5.3.18 glucose - 223 3.5.3.18 glucose 25.5 mmol/l; 25.5 mmol/l 223 3.5.3.18 glycosylated bovine serum albumin - 75596 3.5.3.18 H2O2 43% inhibition at 1 mM 22 3.5.3.18 HgCl2 - 110 3.5.3.18 homocysteine - 747 3.5.3.18 homocysteine inhibition of the expression of DDAH-2 reduces the NO production induced by IL-1beta 747 3.5.3.18 hydrogen peroxide 100 microM, 50% relative activity 1126 3.5.3.18 hyperglycemia - 39105 3.5.3.18 iodoacetamide pH dependent DDAH inactivation, addition of 2.5 mM NG-methyl-L-arginine at pH 8.5 can prevent inactivation by idoacetamide, inactivation may be due to modification at the active site of DDAH, inactivation increases at higher pH values 67 3.5.3.18 l-257 - 204377 3.5.3.18 L-arginine 0.1 mM L-arginine competitively inhibits DDAH enzyme activity to 5.6% 123 3.5.3.18 L-arginine - 123 3.5.3.18 L-citrulline competitive 938 3.5.3.18 L-citrulline - 938 3.5.3.18 L-homocysteine - 305 3.5.3.18 L-lysine competitive inhibitor; potential competitive inhibitor 134 3.5.3.18 leupeptin NG,NG-dimethyl-L-arginine release from freeze-thaw whole blood 55% inhibited 217 3.5.3.18 lipopolysaccharide 1 microg/ml, 24 h, about 55% relative activity; 1 microg/ml, about 55% relative activity 890 3.5.3.18 low-density-lipoprotein 100 microg/ml 75597 3.5.3.18 lysophosphatidylcholine - 695 3.5.3.18 lysophosphatidylcholine activity is significantly decreased in cells treated with lysophosphatidylcholine (0.005 mg/ml) for 48 h, 0.001-0.005 mM probucol or 0.001 mM pyrrolidindithiocarbamate significantly attenuate inhibition of DDAH activity by lysophosphatidylcholine 695 3.5.3.18 lysophosphatidylcholine 10 microg/ml, about 35% relative activity 695 3.5.3.18 Mercuric chloride - 5577 3.5.3.18 methylamine 10 mM, 80% of activity 324 3.5.3.18 monocrotaline DDAH activity and DDAH1, but not DDAH2, protein expression are significantly reduced after 60mg/kg monocrotaline treatment 13488 3.5.3.18 additional information not inhibited by 2-chloroacetamide 2 3.5.3.18 additional information incubation of lysed red blood cells with EDTA or glucose failed to attenuate the degradation of NG,NG-dimethyl-L-arginine, incubation of whole blood cells with arginine methyltransferase inhibitors does not reduce NG,NG-dimethyl-L-arginine release 2 3.5.3.18 additional information probucol or pyrrolidindithiocarbamate itself have no effect on the activity of DDAH 2 3.5.3.18 additional information 5 mM of L-cysteine, L-homocysteine, glutathione, dithiothreitol, or Tris(2-carboxyethyl)phosphine-HCl for 30 min at 37°C cannot restore inhibited activity, suggesting that the covalent product N-thiosulfoximide will remain stable under the reducing conditions present in the cytosol 2 3.5.3.18 additional information exposure to pathophysiological levels of reactive oxygen has little to no effect on the activity of the enzyme 2 3.5.3.18 additional information insensitive to hydrogen peroxide 2 3.5.3.18 additional information tissue-specific decrease of levels of Ddah1 and Ddah2 RNA after feeding a high-methionine/low-folate diet for 5 to 11 month 2 3.5.3.18 additional information decrease of DDAH-2 mRNA level induced by 10% serum, ionomycin or endothelial growth factors 2 3.5.3.18 additional information S-ethyl-2-thiopseudourea, S-ethyl-N-phenylisothiourea and phenylene-1,3-bis(ethane-2-isothiourea) do not inhibit DDAH-1 at concentrations below 1 mM 2 3.5.3.18 N(G)-nitro-L-arginine methyl ester reduced DDAH-2 mRNA level 151878 3.5.3.18 N-(2-methoxyethyl)-L-arginine complete inhibition at 100 microM; complete inhibition at 100 microM 75594 3.5.3.18 N-(2-methoxyethyl)arginine - 75592 3.5.3.18 N-(2-methoxyethyl)arginine methyl esther - 75593 3.5.3.18 N-(but-3-yn-1-yl)-2-chloroethanimidamide click chemistry mediated in vivo activity probe that labels the active fraction of DDAH-1 in intact mammalian cells and that can be blocked by the presence of competitive reversible and irreversible inhibitors 81992 3.5.3.18 N-nitro-L-arginine methylester 1 mM, 1 h, 47.1% relative activity; 1mM, 1 h, 47.1% relative activity 8807 3.5.3.18 N-nitro-L-arginine methylester 1mM, 1 h, 47.1% relative activity 8807 3.5.3.18 N-nitro-L-arginine methylester - 8807 3.5.3.18 N-nitro-L-arginine methylester 1 mM, 1 h, 47.1% relative activity 8807 3.5.3.18 N5-(1-iminoethyl)-L-ornithine - 83749 3.5.3.18 N5-(1-iminohexyl)-L-ornithine - 83752 3.5.3.18 N5-(1-iminopentyl)-L-ornithine - 83751 3.5.3.18 N5-(1-iminopropyl)-L-ornithine crystallization data. Reversible competitive inhibition, consistent with a reversible covalent mode of DDAH inhibition by alkylamidine inhibitors 83750 3.5.3.18 N5-(but-3-en-1-ylcarbamimidoyl)-L-ornithine 1 mM, 71% inhibition 38705 3.5.3.18 N5-(nitrocarbamimidoyl)-L-ornithine 1 mM, 6% inhibition 150757 3.5.3.18 N5-(prop-2-en-1-ylcarbamimidoyl)-L-ornithine 1 mM, 70% inhibition 38706 3.5.3.18 N5-(prop-2-yn-1-ylcarbamimidoyl)-L-ornithine 1 mM, 83% inhibition 38707 3.5.3.18 N5-(propylcarbamimidoyl)-L-ornithine 1 mM, 60% inhibition 38708 3.5.3.18 N5-but-3-enimidoyl-L-ornithine 1 mM, 97% inhibition 38709 3.5.3.18 N5-butanimidoyl-L-ornithine 1 mM, 78% inhibition 38710 3.5.3.18 N5-ethanimidoyl-L-ornithine 1 mM, 24% inhibition 150758 3.5.3.18 N5-propanimidoyl-L-ornithine 1 mM, 65% inhibition 38711 3.5.3.18 N5-[(2,2,2-trifluoroethyl)carbamimidoyl]-L-ornithine 1 mM, 41% inhibition 150320 3.5.3.18 N5-[(2-methoxyethyl)carbamimidoyl]-L-ornithine 1 mM, 89% inhibition 38615 3.5.3.18 N5-[(3-amino-3-oxopropyl)carbamimidoyl]-L-ornithine 1 mM, 43% inhibition 150759 3.5.3.18 N5-[(3E)-pent-3-enimidoyl]-L-ornithine 1 mM, 73% inhibition 38712 3.5.3.18 N5-[imino(morpholin-4-yl)methyl]-L-ornithine 1 mM, 23% inhibition 150760 3.5.3.18 NEM - 89 3.5.3.18 Nicotine 50% decrease in DDAH-2 mRNA 2572 3.5.3.18 nitric oxide - 662 3.5.3.18 nitric oxide increased NO production nitrosates DDAH 662 3.5.3.18 nitrite 1 mM 168 3.5.3.18 nitroglycerine 10 microM, 16 h, about 55% relative activity; 10 microM, about 55% relative activity 38206 3.5.3.18 OH radical 47% inhibition at 1 mM 144051 3.5.3.18 oxidized-low density lipoprotein - 60962 3.5.3.18 oxidized-low density lipoprotein activity is significantly decreased in cells treated with oxidized-low density lipoprotein (0.1 mg/ml) for 48 h, 0.001-0.005 mM probucol or 0.001 mM pyrrolidindithiocarbamat significantly attenuate inhibition of DDAH activity by oxidized-low density lipoprotein 60962 3.5.3.18 PCMB - 78 3.5.3.18 PD 404182 i.e. 6H-6-imino-(2,3,4,5-tetrahydropyrimido)[1,2-c]-[1,3]benzothiazine, potent active-site competitive inhibitor, about 75% inhibition at 0.05 mM 204376 3.5.3.18 pentafluorophenyl sulfonates between 30-76% DDAH inhibition depending on molecular structure of the pentafluoropenyl sulfonate 132657 3.5.3.18 peroxynitrite inhibition of 15% after exposure to peroxynitrite at concentrations ranging from 0.01-0.1 mM, 25% inhibition at 1 mM 1220 3.5.3.18 peroxynitrite - 1220 3.5.3.18 PMSF NG,NG-dimethyl-L-arginine release from freeze-thaw whole blood 57% inhibited 248 3.5.3.18 protease inhibitor NG,NG-dimethyl-L-arginine release from freeze-thaw whole blood 25-85% inhibited 51889 3.5.3.18 S-2-amino-4(3-methylguanidino)butanoic acid - 49409 3.5.3.18 S-2-amino-4-[N-(2-methoxyethyl)guanidino]butanoic acid benzyl ester - 75595 3.5.3.18 S-nitroso-L-cysteine 9-15% inhibition of the zinc-free enzyme at 0.5 mM, S-nitrosylation of the active site Cys273 in DDAH-1 22674 3.5.3.18 S-nitroso-L-homocysteine - 9907 3.5.3.18 S-nitroso-L-homocysteine 96% inhibition of the zinc-free enzyme at 0.5 mM, leads to the unique formation of an N-thiosulfoximide 9907 3.5.3.18 sulfurosalicylic acid inactivates DDAH 132658 3.5.3.18 TNF-alpha 250 U/ml, 63% relative activity 1998 3.5.3.18 Zinc acetate - 10811 3.5.3.18 Zn2+ besides the tightly bound zinc, additional Zn2+ inhibit competitively 14 3.5.3.18 Zn2+ - 14 3.5.3.18 Zn2+ endogenous inhibitor, regulatory role 14 3.5.3.18 Zn2+ one mol per mol of enzyme, apo-enzyme is active, holoenzyme is activated by removal of Zn2+ 14 3.5.3.18 Zn2+ incubation of lysed red blood cells, diminished hydrolyis of NG,NG-dimethyl-L-arginine by addition of physiologically relevant concentrations (0.02 mM) 14 3.5.3.18 Zn2+ 20 microM, 40% relative activity; 20 microM, 40% relative activity 14