1h70: Difference between revisions

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==Overview==

Nitric oxide synthase is inhibited by asymmetric NG-methylated derivatives, of arginine whose cellular levels are controlled in part by, dimethylarginine dimethylaminohydrolase (DDAH, EC 3.5.3.18). Levels of, asymmetric NG,NG-dimethylarginine (ADMA) are known to correlate with, certain disease states. Here, the first structure of a DDAH shows an, unexpected similarity to arginine:glycine amidinotransferase (EC 2.1.4.1), and arginine deiminase (EC 3.5.3.6), thus defining a superfamily of, arginine-modifying enzymes. The identification of a Cys-His-Glu catalytic, triad and the structures of a Cys to Ser point mutant bound to both, substrate and product suggest a reaction mechanism. Comparison of the, ADMA-DDAH and arginine-amidinotransferase complexes reveals a dramatic, rotation of the substrate that effectively maintains the orientation of, the scissile bond of the substrate with respect to the catalytic residues., The DDAH structure will form a basis for the rational design of selective, inhibitors, which are of potential use in modulating NO synthase activity, in pathological settings.

Nitric oxide synthase is inhibited by asymmetric NG-methylated derivatives of arginine whose cellular levels are controlled in part by dimethylarginine dimethylaminohydrolase (DDAH, EC 3.5.3.18). Levels of asymmetric NG,NG-dimethylarginine (ADMA) are known to correlate with certain disease states. Here, the first structure of a DDAH shows an unexpected similarity to arginine:glycine amidinotransferase (EC 2.1.4.1) and arginine deiminase (EC 3.5.3.6), thus defining a superfamily of arginine-modifying enzymes. The identification of a Cys-His-Glu catalytic triad and the structures of a Cys to Ser point mutant bound to both substrate and product suggest a reaction mechanism. Comparison of the ADMA-DDAH and arginine-amidinotransferase complexes reveals a dramatic rotation of the substrate that effectively maintains the orientation of the scissile bond of the substrate with respect to the catalytic residues. The DDAH structure will form a basis for the rational design of selective inhibitors, which are of potential use in modulating NO synthase activity in pathological settings.

==About this Structure==

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[[Category: nitric oxide synthase inhibitor]]

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@@ Line 4: / Line 4: @@
 ==Overview==
-Nitric oxide synthase is inhibited by asymmetric NG-methylated derivatives, of arginine whose cellular levels are controlled in part by, dimethylarginine dimethylaminohydrolase (DDAH, EC 3.5.3.18). Levels of, asymmetric NG,NG-dimethylarginine (ADMA) are known to correlate with, certain disease states. Here, the first structure of a DDAH shows an, unexpected similarity to arginine:glycine amidinotransferase (EC 2.1.4.1), and arginine deiminase (EC 3.5.3.6), thus defining a superfamily of, arginine-modifying enzymes. The identification of a Cys-His-Glu catalytic, triad and the structures of a Cys to Ser point mutant bound to both, substrate and product suggest a reaction mechanism. Comparison of the, ADMA-DDAH and arginine-amidinotransferase complexes reveals a dramatic, rotation of the substrate that effectively maintains the orientation of, the scissile bond of the substrate with respect to the catalytic residues., The DDAH structure will form a basis for the rational design of selective, inhibitors, which are of potential use in modulating NO synthase activity, in pathological settings.
+Nitric oxide synthase is inhibited by asymmetric NG-methylated derivatives of arginine whose cellular levels are controlled in part by dimethylarginine dimethylaminohydrolase (DDAH, EC 3.5.3.18). Levels of asymmetric NG,NG-dimethylarginine (ADMA) are known to correlate with certain disease states. Here, the first structure of a DDAH shows an unexpected similarity to arginine:glycine amidinotransferase (EC 2.1.4.1) and arginine deiminase (EC 3.5.3.6), thus defining a superfamily of arginine-modifying enzymes. The identification of a Cys-His-Glu catalytic triad and the structures of a Cys to Ser point mutant bound to both substrate and product suggest a reaction mechanism. Comparison of the ADMA-DDAH and arginine-amidinotransferase complexes reveals a dramatic rotation of the substrate that effectively maintains the orientation of the scissile bond of the substrate with respect to the catalytic residues. The DDAH structure will form a basis for the rational design of selective inhibitors, which are of potential use in modulating NO synthase activity in pathological settings.
 ==About this Structure==
@@ Line 27: / Line 27: @@
 [[Category: nitric oxide synthase inhibitor]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 09:47:10 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:58:07 2008''