1RXX

Structure of arginine deiminase

Summary for 1RXX

• Entry DOI: 10.2210/pdb1rxx/pdb
• Descriptor: Arginine deiminase (2 entities in total)
• Functional Keywords: arginine degradation pathway, l-arginine deiminase, catalytic mechanism, structure 2 function project, s2f, structural genomics, hydrolase
• Biological source: Pseudomonas aeruginosa
• Cellular location: Cytoplasm (Potential): P13981
• Total number of polymer chains: 4
• Total formula weight: 189156.03

Authors

Galkin, A.,Kulakova, L.,Sarikaya, E.,Lim, K.,Howard, A.,Herzberg, O.,Structure 2 Function Project (S2F) (deposition date: 2003-12-18, release date: 2004-01-13, Last modification date: 2024-11-06)

Primary citation

Galkin, A.,Kulakova, L.,Sarikaya, E.,Lim, K.,Howard, A.,Herzberg, O.
Structural insight into arginine degradation by arginine deiminase, an antibacterial and parasite drug target.
J.Biol.Chem., 279:14001-14008, 2004

PubMed Abstract: l-Arginine deiminase (ADI) catalyzes the irreversible hydrolysis of arginine to citrulline and ammonia. ADI is involved in the first step of the most widespread anaerobic route of arginine degradation. ADI, missing in high eukaryotes, is a potential antimicrobial and antiparasitic drug target. We have determined the crystal structure of ADI from Pseudomonas aeruginosa by the multi-wavelength anomalous diffraction method at 2.45 A resolution. The structure exhibits similarity to other arginine-modifying or substituted arginine-modifying enzymes such as dimethylarginine dimethylaminohydrolase (DDAH), arginine:glycine amidinotransferase, and arginine:inosamine-phosphate amidinotransferase, despite the lack of significant amino acid sequence homology to these enzymes. The similarity spans a core domain comprising five betabetaalphabeta motifs arranged in a circle around a 5-fold pseudosymmetry axis. ADI contains an additional alpha-helical domain of novel topology inserted between the first and the second betabetaalphabeta modules. A catalytic triad, Cys-His-Glu/Asp (arranged in a different manner from that of the thiol proteases), seen in the other arginine-modifying enzymes is also conserved in ADI, as well as many other residues involved in substrate binding. Based on this conservation pattern and the assumption that the substrate binding mode is similar to that of DDAH, an ADI catalytic mechanism is proposed. The main players are Cys-406, which mounts the nucleophilic attack on the carbon atom of the guanidinium group of arginine, and His-278, which serves as a general base.

PubMed: 14701825
DOI: 10.1074/jbc.M313410200

Experimental method

X-RAY DIFFRACTION (2.45 Å)