1rxx
From Proteopedia
(New page: 200px<br /><applet load="1rxx" size="450" color="white" frame="true" align="right" spinBox="true" caption="1rxx, resolution 2.45Å" /> '''Structure of arginin...) |
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| - | [[Image:1rxx.gif|left|200px]]<br /><applet load="1rxx" size=" | + | [[Image:1rxx.gif|left|200px]]<br /><applet load="1rxx" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1rxx, resolution 2.45Å" /> | caption="1rxx, resolution 2.45Å" /> | ||
'''Structure of arginine deiminase'''<br /> | '''Structure of arginine deiminase'''<br /> | ||
==Overview== | ==Overview== | ||
| - | l-Arginine deiminase (ADI) catalyzes the irreversible hydrolysis of | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1RXX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Active as [http://en.wikipedia.org/wiki/Arginine_deiminase Arginine deiminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.6 3.5.3.6] Full crystallographic information is available from [http:// | + | 1RXX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Active as [http://en.wikipedia.org/wiki/Arginine_deiminase Arginine deiminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.6 3.5.3.6] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RXX OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Kulakova, L.]] | [[Category: Kulakova, L.]] | ||
[[Category: Lim, K.]] | [[Category: Lim, K.]] | ||
| - | [[Category: S2F, Structure | + | [[Category: S2F, Structure 2.Function Project.]] |
[[Category: Sarikaya, E.]] | [[Category: Sarikaya, E.]] | ||
[[Category: arginine degradation pathway]] | [[Category: arginine degradation pathway]] | ||
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[[Category: x-ray structure]] | [[Category: x-ray structure]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:55:44 2008'' |
Revision as of 12:55, 21 February 2008
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Structure of arginine deiminase
Overview
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.
About this Structure
1RXX is a Single protein structure of sequence from Pseudomonas aeruginosa. Active as Arginine deiminase, with EC number 3.5.3.6 Full crystallographic information is available from OCA.
Reference
Structural insight into arginine degradation by arginine deiminase, an antibacterial and parasite drug target., Galkin A, Kulakova L, Sarikaya E, Lim K, Howard A, Herzberg O, J Biol Chem. 2004 Apr 2;279(14):14001-8. Epub 2003 Dec 30. PMID:14701825
Page seeded by OCA on Thu Feb 21 14:55:44 2008
Categories: Arginine deiminase | Pseudomonas aeruginosa | Single protein | Galkin, A. | Herzberg, O. | Howard, A. | Kulakova, L. | Lim, K. | S2F, Structure 2.Function Project. | Sarikaya, E. | Arginine degradation pathway | Catalytic mechanism | L-arginine deiminase | S2f | Structural genomics | Structure 2 function project | X-ray structure
