1H70: DDAH FROM PSEUDOMONAS AERUGINOSA. C249S MUTANT COMPLEXED WITH CITRULLINE

Citation:
Abstract
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.
PDB ID: 1H70Download
MMDB ID: 16859
PDB Deposition Date: 2001/6/30
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
Similar Structures:
Biological Unit for 1H70: monomeric; determined by author and by software (PQS)
Molecular Components in 1H70
Label Count Molecule
Protein (1 molecule)
1
NG, Ng-dimethylarginine Dimethylaminohydrolase(Gene symbol: PA1195)
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

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