5OAE

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

5OAE の概要

• エントリーDOI: 10.2210/pdb5oae/pdb
• 分子名称: Tyrosinase, COPPER (II) ION, 1-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]ethanone, ... (4 entities in total)
• 機能のキーワード: tyrosinase inhibitor ligand, oxidoreductase
• 由来する生物種: Bacillus megaterium
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 67303.31

構造登録者

Deri, B.,Gitto, R.,Pazy Benhar, Y.,Fishman, A. (登録日: 2017-06-21, 公開日: 2018-04-25, 最終更新日: 2024-01-17)

主引用文献

Ferro, S.,Deri, B.,Germano, M.P.,Gitto, R.,Ielo, L.,Buemi, M.R.,Certo, G.,Vittorio, S.,Rapisarda, A.,Pazy, Y.,Fishman, A.,De Luca, L.
Targeting Tyrosinase: Development and Structural Insights of Novel Inhibitors Bearing Arylpiperidine and Arylpiperazine Fragments.
J. Med. Chem., 61:3908-3917, 2018

PubMed Abstract: The inhibition of tyrosinase (Ty, EC 1.14.18.1) represents an efficient strategy of decreasing melanogenesis and skin hyperpigmentation. A combination of crystallographic and docking studies on two different tyrosinases, that from Bacillus megaterium (TyBm) and that from a mushroom (TyM), has contributed to increasing our knowledge about their structural information and translating that information to the most druggable human Ty (TyH) isozyme. In particular, we designed and synthesized a series of 1-(4-fluorobenzyl)piperazine and 1-(4-fluorobenzyl)piperidine derivatives showing inhibitory activities on TyM at micromolar ranges and more potency than that of the reference compound, kojic acid. The crystal structures of TyBm with inhibitor 3 (IC value of 25.11 μM) and 16 (IC value of 5.25 μM) were solved, confirming the binding poses hypothesized by in silico studies and revealing the main molecular determinants for the binding recognition of the inhibitors.

PubMed: 29634898
DOI: 10.1021/acs.jmedchem.7b01745

実験手法

X-RAY DIFFRACTION (2.7 Å)