1D3V
CRYSTAL STRUCTURE OF THE BINUCLEAR MANGANESE METALLOENZYME ARGINASE COMPLEXED WITH 2(S)-AMINO-6-BORONOHEXANOIC ACID, AN L-ARGININE ANALOG
Summary for 1D3V
| Entry DOI | 10.2210/pdb1d3v/pdb |
| Descriptor | PROTEIN (ARGINASE), MANGANESE (II) ION, 2(S)-AMINO-6-BORONOHEXANOIC ACID, ... (4 entities in total) |
| Functional Keywords | binuclear manganese cluster, boronic acid inhibitor, perfectly twinned crystal, hydrolase |
| Biological source | Rattus norvegicus (Norway rat) |
| Cellular location | Cytoplasm: P07824 |
| Total number of polymer chains | 2 |
| Total formula weight | 70641.94 |
| Authors | Cox, J.D.,Kim, N.N.,Traish, A.M.,Christianson, D.W. (deposition date: 1999-10-01, release date: 1999-11-17, Last modification date: 2024-02-07) |
| Primary citation | Cox, J.D.,Kim, N.N.,Traish, A.M.,Christianson, D.W. Arginase-boronic acid complex highlights a physiological role in erectile function. Nat.Struct.Biol., 6:1043-1048, 1999 Cited by PubMed Abstract: The crystal structure of the complex between the binuclear manganese metalloenzyme arginase and the boronic acid analog of L-arginine, 2(S)-amino-6-boronohexanoic acid (ABH), has been determined at 1.7 A resolution from a crystal perfectly twinned by hemihedry. ABH binds as the tetrahedral boronate anion, with one hydroxyl oxygen symmetrically bridging the binuclear manganese cluster and a second hydroxyl oxygen coordinating to Mn2+A. This binding mode mimics the transition state of a metal-activated hydroxide mechanism. This transition state structure differs from that occurring in NO biosynthesis, thereby explaining why ABH does not inhibit NO synthase. We also show that arginase activity is present in the penis. Accordingly, the tight binding and specificity of ABH allows us to probe the physiological role of arginase in modulating the NO-dependent smooth muscle relaxation required for erection. Strikingly, ABH causes significant enhancement of nonadrenergic, noncholinergic nerve-mediated relaxation of penile corpus cavernosum smooth muscle, suggesting that arginase inhibition sustains L-arginine concentrations for NO synthase activity. Therefore, human penile arginase is a potential target for therapeutic intervention in the treatment of erectile dysfunction. PubMed: 10542097DOI: 10.1038/14929 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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