1t5g
Arginase-F2-L-Arginine complex
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OverviewOverview
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.
About this StructureAbout this Structure
1T5G is a Single protein structure of sequence from Rattus norvegicus with F, MN and ARG as ligands. Active as Arginase, with EC number 3.5.3.1 Full crystallographic information is available from OCA.
ReferenceReference
Inhibitor coordination interactions in the binuclear manganese cluster of arginase., Cama E, Pethe S, Boucher JL, Han S, Emig FA, Ash DE, Viola RE, Mansuy D, Christianson DW, Biochemistry. 2004 Jul 20;43(28):8987-99. PMID:15248756
Page seeded by OCA on Wed Nov 21 03:00:21 2007