1T4T
arginase-dinor-NOHA complex
Summary for 1T4T
Entry DOI | 10.2210/pdb1t4t/pdb |
Related | 1HQF 1T4P 1T4R 1T4S 1T5F 1T5G |
Descriptor | Arginase 1, MANGANESE (II) ION, 3-{[(E)-AMINO(HYDROXYIMINO)METHYL]AMINO}ALANINE, ... (4 entities in total) |
Functional Keywords | arginase, dinor-noha, hydrolase |
Biological source | Rattus norvegicus (Norway rat) |
Cellular location | Cytoplasm: P07824 |
Total number of polymer chains | 3 |
Total formula weight | 102920.66 |
Authors | Cama, E.,Pethe, S.,Boucher, J.-L.,Shoufa, H.,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 Cited by 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: 15248756DOI: 10.1021/bi0491705 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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