6RRP

Crystal structure of tyrosinase PvdP from Pseudomonas aeruginosa bound to copper and phenylthiourea

6RRP の概要

• エントリーDOI: 10.2210/pdb6rrp/pdb
• 分子名称: PvdP, N-PHENYLTHIOUREA, COPPER (II) ION, ... (4 entities in total)
• 機能のキーワード: tyrosinase, pyoverdine, copper, inhibitor, phenylthiourea, oxidoreductase
• 由来する生物種: Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 125322.83

構造登録者

Wibowo, J.P.,Batista, F.A.,van Oosterwijk, N.,Groves, M.R.,Dekker, F.J.,Quax, W.J. (登録日: 2019-05-20, 公開日: 2020-04-15, 最終更新日: 2024-01-24)

主引用文献

Wibowo, J.P.,Batista, F.A.,van Oosterwijk, N.,Groves, M.R.,Dekker, F.J.,Quax, W.J.
A novel mechanism of inhibition by phenylthiourea on PvdP, a tyrosinase synthesizing pyoverdine of Pseudomonas aeruginosa.
Int.J.Biol.Macromol., 146:212-221, 2020

PubMed Abstract: The biosynthesis of pyoverdine, the major siderophore of Pseudomonas aeruginosa, is a well-organized process involving a discrete number of enzyme-catalyzed steps. The final step of this process involves the PvdP tyrosinase, which converts ferribactin into pyoverdine. Thus, inhibition of the PvdP tyrosinase activity provides an attractive strategy to interfere with siderophore synthesis to manage P. aeruginosa infections. Here, we report phenylthiourea as a non-competitive inhibitor of PvdP for which we solved a crystal structure in complex with PvdP. The crystal structure indicates that phenylthiourea binds to an allosteric binding site and thereby interferes with its tyrosinase activity. We further provide proofs that PvdP tyrosinase inhibition by phenylthiourea requires the C-terminal lid region. This provides opportunities to develop inhibitors that target the allosteric site, which seems to be confined to fluorescent pseudomonads, and not the tyrosinase active site. Furthermore, increases the chances to identify PvdP inhibitors that selectively interfere with siderophore synthesis.

PubMed: 31899238
DOI: 10.1016/j.ijbiomac.2019.12.252

実験手法

X-RAY DIFFRACTION (2.4 Å)