1h70: Difference between revisions
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==Overview== | ==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 .. | 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== | ==About this Structure== | ||
1H70 is a | 1H70 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa] with CIR as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Dimethylargininase Dimethylargininase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.18 3.5.3.18] Structure known Active Site: CIR. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1H70 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: nitric oxide synthase inhibitor]] | [[Category: nitric oxide synthase inhibitor]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 12:34:07 2007'' | ||
