1h70

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{{STRUCTURE_1h70| PDB=1h70 | SCENE= }}
{{STRUCTURE_1h70| PDB=1h70 | SCENE= }}
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'''DDAH FROM PSEUDOMONAS AERUGINOSA. C249S MUTANT COMPLEXED WITH CITRULLINE'''
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===DDAH FROM PSEUDOMONAS AERUGINOSA. C249S MUTANT COMPLEXED WITH CITRULLINE===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 11473257 is the PubMed ID number.
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{{ABSTRACT_PUBMED_11473257}}
==About this Structure==
==About this Structure==
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[[Category: Hydrolase]]
[[Category: Hydrolase]]
[[Category: Nitric oxide synthase inhibitor]]
[[Category: Nitric oxide synthase inhibitor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:30:56 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 06:43:47 2008''

Revision as of 03:43, 1 July 2008

Template:STRUCTURE 1h70

DDAH FROM PSEUDOMONAS AERUGINOSA. C249S MUTANT COMPLEXED WITH CITRULLINE

Template:ABSTRACT PUBMED 11473257

About this Structure

1H70 is a Single protein structure of sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA.

Reference

Structural insights into the hydrolysis of cellular nitric oxide synthase inhibitors by dimethylarginine dimethylaminohydrolase., Murray-Rust J, Leiper J, McAlister M, Phelan J, Tilley S, Santa Maria J, Vallance P, McDonald N, Nat Struct Biol. 2001 Aug;8(8):679-83. PMID:11473257

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