6qxd | pdb_00006qxd

Crystal Structure of tyrosinase from Bacillus megaterium with JKB inhibitor in the active site.

spinqualitylabelsall models 6qxd, resolution 2.32Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6qxd is a 2 chain structure with sequence from Priestia megaterium. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.317Å Ligands: CU, JKB Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function B2ZB02_PRIMG Publication Abstract from PubMed 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 (IC50=0.96muM) proved to be approximately 20-fold more potent than the reference compound kojic acid (IC50=17.76muM) 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. 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.,Ielo L, Deri B, Germano MP, Vittorio S, Mirabile S, Gitto R, Rapisarda A, Ronsisvalle S, Floris S, Pazy Y, Fais A, Fishman A, De Luca L Eur J Med Chem. 2019 Jun 6;178:380-389. doi: 10.1016/j.ejmech.2019.06.019. PMID:31202126 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Tyrosinase 3D structures

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