6QXD
Crystal Structure of tyrosinase from Bacillus megaterium with JKB inhibitor in the active site.
Summary for 6QXD
| Entry DOI | 10.2210/pdb6qxd/pdb |
| Descriptor | Tyrosinase, COPPER (II) ION, (2,4-dinitrophenyl)-[4-[(4-fluorophenyl)methyl]piperazin-1-yl]methanone, ... (4 entities in total) |
| Functional Keywords | tyrosinase, inhibitor, ligand, oxidoreductase |
| Biological source | Bacillus megaterium |
| Total number of polymer chains | 2 |
| Total formula weight | 67221.07 |
| Authors | Deri Zenaty, B.,Gitto, R.,Pazy, Y.,Fishman, A. (deposition date: 2019-03-07, release date: 2019-06-19, Last modification date: 2024-01-24) |
| Primary citation | Ielo, L.,Deri, B.,Germano, M.P.,Vittorio, S.,Mirabile, S.,Gitto, R.,Rapisarda, A.,Ronsisvalle, S.,Floris, S.,Pazy, Y.,Fais, A.,Fishman, A.,De Luca, L. Exploiting the 1-(4-fluorobenzyl)piperazine fragment for the development of novel tyrosinase inhibitors as anti-melanogenic agents: Design, synthesis, structural insights and biological profile. Eur.J.Med.Chem., 178:380-389, 2019 Cited by PubMed Abstract: The development of Tyrosinase inhibitors (TYRIs) could represent an efficacious strategy for pharmacological intervention on skin pathologies related to aberrant production of melanin. Based on in silico studies we designed and tested a library of twenty-four compounds bearing the 4-(4-fluorobenzyl)piperazin-1-yl]-fragment. As result, we identified several compounds with excellent inhibit effects at low micromolar concentration against TYR from Agaricus bisporus (TyM). Among them, compound 25 (IC = 0.96 μM) proved to be ∼20-fold more potent than the reference compound kojic acid (IC = 17.76 μM) having wide applications in the cosmetics and pharmaceutical industries. The mode of interaction of active inhibitor 25 was deciphered by means of crystallography as well as molecular docking and these results were consistent with kinetic experiments. Moreover, the identified compound 25 exhibited no considerable cytotoxicity and showed anti-melanogenic effects on B16F10 melanoma cells. Therefore, a combination of computational and biochemical approaches could represent a rational guidelines for further structural modification of this class of compounds as future anti-melanogenic agents. PubMed: 31202126DOI: 10.1016/j.ejmech.2019.06.019 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.317 Å) |
Structure validation
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