Sandbox Reserved 322: Difference between revisions
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Overall arginase is a homotrimeric metallo-enzyme with a binuclear manganese <scene name='Sandbox_Reserved_322/Mn/5'>MN</scene> cluster in each monomer as shown in the PDB identifier 3mmr<ref name="c"/>. The overall fold of the arginase monomer belongs to the α/β protein class with a globular structure<ref name="d">PMID: 8849731 </ref>. | Overall arginase is a homotrimeric metallo-enzyme with a binuclear manganese <scene name='Sandbox_Reserved_322/Mn/5'>MN</scene> cluster in each monomer as shown in the PDB identifier 3mmr<ref name="c"/>. The overall fold of the arginase monomer belongs to the α/β protein class with a globular structure<ref name="d">PMID: 8849731 </ref>. | ||
One site of the active-site cleft is partially defined by the central 8-stranded <scene name='Sandbox_Reserved_322/8-stranded_beta-sheet/1'>β-sheet</scene>, and the <scene name='Sandbox_Reserved_322/Metal_binding_sites/1'>metal binding sites</scene> is located on the edge of the β-sheet<ref name="d"/>. The metal ion that is more deeply situated in the active-site cleft is designated <scene name='Sandbox_Reserved_322/ | One site of the active-site cleft is partially defined by the central 8-stranded <scene name='Sandbox_Reserved_322/8-stranded_beta-sheet/1'>β-sheet</scene>, and the <scene name='Sandbox_Reserved_322/Metal_binding_sites/1'>metal binding sites</scene> is located on the edge of the β-sheet<ref name="d"/>. The metal ion that is more deeply situated in the active-site cleft is designated <scene name='Sandbox_Reserved_322/Mn2a/1'>Mn2+A</scene> while the other metal ion is designated Mn<sup>2+</sup><sub>B</sub>. In ''Plasmodium falciparum'' arginase Mn<sup>2+</sup><sub>A</sub> is coordinated by <scene name='Sandbox_Reserved_322/Mna/1'>His 193, Asp 216, Asp 220, Asp 323</scene> and a solvent molecule, with a square pyramidal geometry<ref name="b"/><ref name="d"/>. The solvent molecule bridges both metal ions and also donates a hydrogen bond to Asp 220<ref name="b"/><ref name="d"/>. Mn<sup>2+</sup><sub>B</sub> is coordinated by <scene name='Sandbox_Reserved_322/Mnb/1'>His 218, Asp 216, Asp 323, Asp 325</scene> and the bridging solvent molecule in a distorted octahedral fashion<ref name="d"/>. All metal ligands except for Asp 220 make hydrogen-bond interactions with other protein residues, and these interactions contribute to the stability of the metal binding site<ref name="b"/><ref name="d"/>. | ||
There are three different types of bridging metal ligands that facilitate the observed spin coupling between Mn<sup>2+</sup><sub>A</sub> and Mn<sup>2+</sup><sub>B</sub><ref name="d"/>. For the first ligand, the carboxylate side chain of Asp 216 is a syn-syn bidentate bridging ligand, with Oδ1 coordinated to Mn<sup>2+</sup><sub>A</sub> and Oδ2 coordinated to Mn<sup>2+</sup><sub>B</sub><ref name="d"/>. For the second ligand, the carboxylate side chain of Asp 323 is a monodentate bridging ligand, with Oδ1 coordinated to both Mn<sup>2+</sup><sub>A</sub> and Mn<sup>2+</sup><sub>B</sub> with anti- and syn-coordination stereo-chemistry, respectively<ref name="b"/><ref name="d"/>. And finally the third ligand, is the solvent molecule bridges both manganese ion symmetrically<ref name="d"/>. Also the Mn<sup>2+</sup> ions coordinate with water, orienting and stabilizing the molecule and allowing water to act as a nucleophile and attack L-arginine, hydrolyzing it into orinithine and urea<ref name="c"/>. Overall the two manganese metal ion in arginase maintain the proper function of the enzyme<ref name="b"/>. | There are three different types of bridging metal ligands that facilitate the observed spin coupling between Mn<sup>2+</sup><sub>A</sub> and Mn<sup>2+</sup><sub>B</sub><ref name="d"/>. For the first ligand, the carboxylate side chain of Asp 216 is a syn-syn bidentate bridging ligand, with Oδ1 coordinated to Mn<sup>2+</sup><sub>A</sub> and Oδ2 coordinated to Mn<sup>2+</sup><sub>B</sub><ref name="d"/>. For the second ligand, the carboxylate side chain of Asp 323 is a monodentate bridging ligand, with Oδ1 coordinated to both Mn<sup>2+</sup><sub>A</sub> and Mn<sup>2+</sup><sub>B</sub> with anti- and syn-coordination stereo-chemistry, respectively<ref name="b"/><ref name="d"/>. And finally the third ligand, is the solvent molecule bridges both manganese ion symmetrically<ref name="d"/>. Also the Mn<sup>2+</sup> ions coordinate with water, orienting and stabilizing the molecule and allowing water to act as a nucleophile and attack L-arginine, hydrolyzing it into orinithine and urea<ref name="c"/>. Overall the two manganese metal ion in arginase maintain the proper function of the enzyme<ref name="b"/>. | ||