1T4P

Arginase-dehydro-ABH complex

Summary for 1T4P

• Entry DOI: 10.2210/pdb1t4p/pdb
• Related: 1D3V 1T4R 1T4S 1T4T 1T5F 1T5G
• Descriptor: Arginase 1, MANGANESE (II) ION, [(1E,5S)-5-AMINO-5-CARBOXYPENT-1-ENYL](TRIHYDROXY)BORATE(1-), ... (4 entities in total)
• Functional Keywords: arginase, dehydro-abh, hydrolase
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Cytoplasm: P07824
• Total number of polymer chains: 3
• Total formula weight: 103004.16

Authors

Cama, E.,Pethe, S.,Boucher, J.-L.,Han, S.,Emig, F.A.,Ash, D.E.,Viola, R.E.,Mansuy, D.,Christianson, D.W. (deposition date: 2004-04-30, release date: 2005-04-12, Last modification date: 2024-02-14)

Primary citation

Cama, E.,Pethe, S.,Boucher, J.-L.,Han, S.,Emig, F.A.,Ash, D.E.,Viola, R.E.,Mansuy, D.,Christianson, D.W.
Inhibitor coordination interactions in the binuclear manganese cluster of arginase
Biochemistry, 43:8987-8999, 2004

PubMed Abstract: Arginase is a manganese metalloenzyme that catalyzes the hydrolysis of L-arginine to form L-ornithine and urea. The structure and stability of the binuclear manganese cluster are critical for catalytic activity as it activates the catalytic nucleophile, metal-bridging hydroxide ion, and stabilizes the tetrahedral intermediate and its flanking states. Here, we report X-ray structures of a series of inhibitors bound to the active site of arginase, and each inhibitor exploits a different mode of coordination with the Mn(2+)(2) cluster. Specifically, we have studied the binding of fluoride ion (F(-); an uncompetitive inhibitor) and L-arginine, L-valine, dinor-N(omega)-hydroxy-L-arginine, descarboxy-nor-N(omega)-hydroxy-L-arginine, and dehydro-2(S)-amino-6-boronohexanoic acid. Some inhibitors, such as fluoride ion, dinor-N(omega)-hydroxy-L-arginine, and dehydro-2(S)-amino-6-boronohexanoic acid, cause the net addition of one ligand to the Mn(2+)(2) cluster. Other inhibitors, such as descarboxy-nor-N(omega)-hydroxy-L-arginine, simply displace the metal-bridging hydroxide ion of the native enzyme and do not cause any net change in the metal coordination polyhedra. The highest affinity inhibitors displace the metal-bridging hydroxide ion (and sometimes occupy a Mn(2+)(A) site found vacant in the native enzyme) and maintain a conserved array of hydrogen bonds with their alpha-amino and -carboxylate groups.

PubMed: 15248756
DOI: 10.1021/bi0491705

Experimental method

X-RAY DIFFRACTION (2.6 Å)