A Heme‐Acquisition Protein Reconstructed with a Cobalt 5‐Oxaporphyrinium Cation and Its Growth‐Inhibition Activity Toward Multidrug‐Resistant Pseudomonas aeruginosa
A Heme‐Acquisition Protein Reconstructed with a Cobalt 5‐Oxaporphyrinium Cation and Its Growth‐Inhibition Activity Toward Multidrug‐Resistant Pseudomonas aeruginosa
复制标题
用 5-氧代卟啉钴阳离子重建的血红素获取蛋白及其对多重耐药铜绿假单胞菌的生长抑制活性
DOI：
10.1002/anie.202112456
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Shinokubo Hiroshi
中科院分区：
文献类型：
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作者：
Takiguchi Asahi;Sakakibara Erika;Sugimoto Hiroshi;Shoji Osami;Shinokubo Hiroshi
利用人工血红素重构天然血红素蛋白是提高天然血红素蛋白生物活性的一条有效途径。我们报道了多种金属5-氧代卟啉阳离子作为辅助因子的合成，并且将钴5-氧代卟啉阳离子成功地并入铜绿假单胞菌分泌的血红素获取蛋白（HasA）中。我们假设氧卟啉阳离子由于其阳离子电荷而与HasA特异性外膜受体（HasR）强烈结合，这阻止了随后的血红素获取。事实上，重建的HasA抑制了铜绿假单胞菌的生长，甚至抑制了多药耐药的P。铜绿。
Using artificial hemes for the reconstruction of natural heme proteins represents a fascinating approach to enhance the bioactivity of the latter. We report the synthesis of various metal 5‐oxaporphyrinium cations as cofactors, and a cobalt 5‐oxaporphyrinium cation was successfully incorporated into the heme‐acquisition protein (HasA) secreted byPseudomonas aeruginosa. We hypothesize that the oxaporphyrinium cation strongly binds to the HasA‐specific outer membrane receptor (HasR) due to its cationic charge, which prevents the subsequent acquisition of heme. In fact, the reconstructed HasA inhibited the growth ofPseudomonas aeruginosaand even of multidrug‐resistantP. aeruginosa.