Lin Ting-Yu, Nagano Soshichiro, Gardiner Heddle Jonathan
Heddle Initiative Research Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
Sci Rep. 2015 Sep 28;5:14491. doi: 10.1038/srep14491.
A number of important protozoan parasites including those responsible for toxoplasmosis and malaria belong to the phylum Apicomplexa and are characterised by their possession of a relict plastid, the apicoplast. Being required for survival, apicoplasts are potentially useful drug targets and their attractiveness is increased by the fact that they contain "bacterial" gyrase, a well-established antibacterial drug target. We have cloned and purified the gyrase proteins from the apicoplast of Toxoplasma gondii (the cause of toxoplasmosis), reconstituted the functional enzyme and succeeded in characterising it. We discovered that the enzyme is inhibited by known gyrase inhibitors and that, as well as the expected supercoiling activity, it is also able to decatenate DNA with high efficiency. This unusual dual functionality may be related to the apparent lack of topoisomerase IV in the apicoplast.
许多重要的原生动物寄生虫，包括那些导致弓形虫病和疟疾的寄生虫，都属于顶复门，其特征是拥有一种残余质体——顶质体。顶质体是生存所必需的，因此可能是有用的药物靶点，而且由于它们含有“细菌”gyrase（一种成熟的抗菌药物靶点），其吸引力进一步增加。我们已经从弓形虫（弓形虫病的病原体）的顶质体中克隆并纯化了gyrase蛋白，重构了功能酶并成功对其进行了表征。我们发现该酶被已知的gyrase抑制剂抑制，并且除了预期的超螺旋活性外，它还能够高效地解开连环DNA。这种不寻常的双重功能可能与顶质体中明显缺乏拓扑异构酶IV有关。
