7P7O

X-RAY CRYSTAL STRUCTURE OF SPOROSARCINA PASTEURII UREASE INHIBITED BY THE GOLD(I)-DIPHOSPHINE COMPOUND Au(PEt3)2Cl DETERMINED AT 1.87 ANGSTROMS

これはPDB形式変換不可エントリーです。

7P7O の概要

• エントリーDOI: 10.2210/pdb7p7o/pdb
• 分子名称: Urease subunit gamma, Urease subunit beta, Urease subunit alpha, ... (9 entities in total)
• 機能のキーワード: urease, nickel, gold, enzyme, urea, hydrolase
• 由来する生物種: Sporosarcina pasteurii; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 89578.03

構造登録者

Mazzei, L.,Ciurli, S.,Cianci, M.,Messori, L.,Massai, L. (登録日: 2021-07-20, 公開日: 2022-06-01, 最終更新日: 2024-01-31)

主引用文献

Mazzei, L.,Massai, L.,Cianci, M.,Messori, L.,Ciurli, S.
Medicinal Au(I) compounds targeting urease as prospective antimicrobial agents: unveiling the structural basis for enzyme inhibition.
Dalton Trans, 50:14444-14452, 2021

PubMed Abstract: A few gold compounds were recently found to show antimicrobial properties , holding great promise for the discovery of new drugs to overcome antibiotic resistance. Here, the inhibition of the bacterial virulence factor urease by four Au(I)-compounds, namely Au(PEt)Cl, Au(PEt)Br, Au(PEt)I and [Au(PEt)]Cl, obtained from the antiarthritic Au(I)-drug Auranofin and earlier reported to act as antimicrobials, is investigated. The three monophosphino Au(I) complexes showed IC values in the 30-100 nM range, while the diphosphino Au(I) complex, though being less active, still showed a IC value of 7 μM. The structural basis for this inhibition was provided by solving the crystal structures of urease co-crystallized with Au(PEt)I and [Au(PEt)]Cl: at least two Au(I) ions bind the enzyme in a flap domain involved in the catalysis, thus obliterating enzyme activity. Peculiar changes observed in the two structures reveal implications for the mechanism of soft metal binding and enzyme inactivation.

PubMed: 34585201
DOI: 10.1039/d1dt02488d

実験手法

X-RAY DIFFRACTION (1.87 Å)