2CI3

Crystal Structure of Dimethylarginine dimethylaminohydrolase crystal form I

Summary for 2CI3

• Entry DOI: 10.2210/pdb2ci3/pdb
• Related: 2C6Z 2CI1 2CI4 2CI5 2CI6 2CI7
• Descriptor: NG, NG-DIMETHYLARGININE DIMETHYLAMINOHYDROLASE 1 (2 entities in total)
• Functional Keywords: nos regulation, s-nitrosylation, zinc, hydrolase, no, mma, adma
• Biological source: BOS TAURUS (BOVINE)
• Total number of polymer chains: 1
• Total formula weight: 31198.67

Authors

Frey, D.,Braun, O.,Briand, C.,Vasak, M.,Grutter, M.G. (deposition date: 2006-03-17, release date: 2006-05-17, Last modification date: 2023-12-13)

Primary citation

Frey, D.,Braun, O.,Briand, C.,Vasak, M.,Grutter, M.G.
Structure of the Mammalian Nos Regulator Dimethylarginine Dimethylaminohydrolase: A Basis for the Design of Specific Inhibitors.
Structure, 14:901-, 2006

PubMed Abstract: 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.

PubMed: 16698551
DOI: 10.1016/J.STR.2006.03.006

Experimental method

X-RAY DIFFRACTION (1.7 Å)