2CI1: Crystal Structure Of Dimethylarginine Dimethylaminohydrolase I In Complex With S-Nitroso- Lhomocysteine

Dimethylarginine dimethylaminohydrolase (DDAH) is involved in the regulation of nitric oxide synthase (NOS) by metabolizing the free endogenous arginine derivatives N(omega)-methyl-L-arginine (MMA) and N(omega),N(omega)-dimethyl-L-arginine (ADMA), which are competitive inhibitors of NOS. Here, we present high-resolution crystal structures of DDAH isoform 1 (DDAH-1) isolated from bovine brain in complex with different inhibitors, including S-nitroso-L-homocysteine and Zn2+, a regulator of this mammalian enzyme. The structure of DDAH-1 consists of a propeller-like fold similar to other arginine-modifying enzymes and a flexible loop, which adopts different conformations and acts as a lid at the entrance of the active site. The orientation and interaction mode of inhibitors in the active site give insight into the regulation and the molecular mechanism of the enzyme. The presented structures provide a basis for the structure-based development of specific DDAH-1 inhibitors that might be useful in the therapeutic treatment of NOS dysfunction-related diseases.
PDB ID: 2CI1Download
MMDB ID: 52846
PDB Deposition Date: 2006/3/17
Updated in MMDB: 2011/11
Experimental Method:
x-ray diffraction
Resolution: 1.08  Å
Source Organism:
Similar Structures:
Biological Unit for 2CI1: monomeric; determined by author and by software (PQS)
Molecular Components in 2CI1
Label Count Molecule
Protein (1 molecule)
NG, Ng-dimethylarginine Dimethylaminohydrolase 1(Gene symbol: DDAH1)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB