The MmcO protein of Mycobacterium tuberculosis is a membrane-associated multicopper oxidase. Its natural substrate(s) and its role in pathogenesis are not well characterized. A recent report proposes that MmcO contributes to copper resistance in M. tuberculosis during infection. We have expressed and reconstituted the active enzyme from inclusion bodies in E. coli. MmcO exhibits maximal activity against the experimental substrate 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) or ABTS, at pH 4. The enzyme also exhibits ferroxidase activity at pH 4. Most notable was the finding that MmcO is able to scavenge the reactive oxygen species (ROS) generated by the xanthine/xanthine oxidase enzyme system. This ROS scavenging activity of MmcO was also evident against ROS generated by THP-1 cells. We propose that MmcO protects M. tuberculosis during infection against ROS attack in addition to providing copper resistance to the pathogen.

结核分枝杆菌的MmcO蛋白是一种与膜相关的多铜氧化酶。其天然底物及其在发病机理中的作用尚未得到很好的表征。最近的一份报告提出，MmcO在感染过程中有助于结核分枝杆菌的铜抗性。我们已经从大肠杆菌的包涵体中表达并重构了活性酶。MmcO在pH 4时对实验底物2,2'-叠氮基双（3-乙基苯并噻唑啉-6-磺酸）或ABTS表现出最大活性。该酶在pH 4时也表现出铁氧化酶活性。最值得注意的发现是MmcO能够清除由黄嘌呤/黄嘌呤氧化酶系统产生的活性氧（ROS）。MmcO的这种ROS清除活性对于THP-1细胞产生的ROS也很明显。我们提出，MmcO除了为病原体提供铜抗性外，还可以在感染过程中保护结核分枝杆菌免受ROS攻击。