Study of relationship of physiological roles and pathogenicity of aggressive periodontopathic bacterial quinol peroxidase

伴生放线杆菌的喹醇过氧化物酶(QPO)利用呼吸链上的一种喹酚催化过氧化物酶活性。AqPO缺失突变体表现出氧化应激表型，这表明QPO在清除内源产生的过氧化氢方面发挥着重要作用，并显示出白细胞(LtxA)的产生减少，这是一种已知的塔氏白细胞分泌的细菌毒素。筛选证明阿司可呋喃酮是一种高效的QPO抑制剂(Ki=9.6 nM)。该抑制剂还减少了LtxA的分泌，并相关地降低了FA的致病性。放线菌对HL-60细胞的伴生作用。我们在大肠杆菌中成功构建了重组QPO表达系统。用纯化的重组QPO对其催化机理进行了分析，表明QPO的催化机理为乒乓比机理。

Quinol peroxidase (QPO) of Aggregatibacter actinomycetemcomitans catalyzes peroxidase activity using a quinol on respiratory chain.Aqpo null mutant exhibits an oxidative stress phenotype, suggesting that QPO plays animportant role in scavenging endogenously generated hydrogen peroxide, and exhibitsreduced production of leukocyte (LtxA), a secreted bacterial toxin that is known to targethuman leukocytes. Screening identified ascofuranone as a highly potent inhibitor of QPO(Ki = 9.6 nM). This inhibitor also reduced the secretion of LtxA, with an associatedreduction in the pathogenicity ofA. actinomycetemcomitans for HL-60 cells. We producedthe recombinant QPO expression system inEscherichia coli. Purified recombinant QPOwas used to analyse the catalytic mechanism, indicating that QPO catalyzes as ping pongbi bi mechanism.