5HJ9
Crystal structure of Leishmania mexicana arginase in complex with inhibitor ABHPE
Summary for 5HJ9
| Entry DOI | 10.2210/pdb5hj9/pdb |
| Related | 4ITY 5HJA |
| Descriptor | Arginase, MANGANESE (II) ION, [(5R)-5-amino-5-carboxy-7-(piperidin-1-yl)heptyl](trihydroxy)borate(1-), ... (8 entities in total) |
| Functional Keywords | hydrolase |
| Biological source | Leishmania mexicana |
| Total number of polymer chains | 1 |
| Total formula weight | 37122.21 |
| Authors | Hai, Y.,Christianson, D.W. (deposition date: 2016-01-13, release date: 2016-04-13, Last modification date: 2023-09-27) |
| Primary citation | Hai, Y.,Christianson, D.W. Crystal structures of Leishmania mexicana arginase complexed with alpha , alpha-disubstituted boronic amino-acid inhibitors. Acta Crystallogr F Struct Biol Commun, 72:300-306, 2016 Cited by PubMed Abstract: Leishmania arginase is a potential drug target for the treatment of leishmaniasis because this binuclear manganese metalloenzyme initiates de novo polyamine biosynthesis by catalyzing the hydrolysis of L-arginine to generate L-ornithine and urea. The product L-ornithine subsequently undergoes decarboxylation to yield putrescine, which in turn is utilized for spermidine biosynthesis. Polyamines such as spermidine are essential for the growth and survival of the parasite, so inhibition of enzymes in the polyamine-biosynthetic pathway comprises an effective strategy for treating parasitic infections. To this end, two X-ray crystal structures of L. mexicana arginase complexed with α,α-disubstituted boronic amino-acid inhibitors based on the molecular scaffold of 2-(S)-amino-6-boronohexanoic acid are now reported. Structural comparisons with human and parasitic arginase complexes reveal interesting differences in the binding modes of the additional α-substituents, i.e. the D side chains, of these inhibitors. Subtle differences in the three-dimensional contours of the outer active-site rims among arginases from different species lead to different conformations of the D side chains and thus different inhibitor-affinity trends. The structures suggest that it is possible to maintain affinity while fine-tuning intermolecular interactions of the D side chain of α,α-disubstituted boronic amino-acid inhibitors in the search for isozyme-specific and species-specific arginase inhibitors. PubMed: 27050264DOI: 10.1107/S2053230X16003630 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.28 Å) |
Structure validation
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