DevS氧化复合物的稳定性将这种血红素蛋白鉴定为结核分枝杆菌休眠状态下的气体传感器。
DevS oxy complex stability identifies this heme protein as a gas sensor in Mycobacterium tuberculosis dormancy.
作者信息
Ioanoviciu Alexandra, Meharenna Yergalem T, Poulos Thomas L, Ortiz de Montellano Paul R
机构信息
Department of Pharmaceutical Chemistry, University of California, 600 16th Street, San Francisco, California 94158-2517, USA.
出版信息
Biochemistry. 2009 Jun 30;48(25):5839-48. doi: 10.1021/bi802309y.
DevS is one of the two sensing kinases responsible for DevR activation and the subsequent entry of Mycobacterium tuberculosis into dormancy. Full-length wild-type DevS forms a stable oxy-ferrous complex. The DevS autoxidation rates are extremely low (half-lives of >24 h) in the presence of cations such as K(+), Na(+), Mg(2+), and Ca(2+). At relatively high concentrations (100 mM), Cu(2+) accelerates autoxidation more than 1500-fold. Contrary to expectations, removal of the key hydrogen bond between the iron-coordinated oxygen and Tyr171 in the Y171F mutant provides a protein of comparable stability to autoxidation and similar oxygen dissociation rate. This correlates with our earlier finding that the Y171F mutant and wild-type kinase activities are similarly regulated by the binding of oxygen: namely, the ferrous five-coordinate complex is active, whereas the oxy-ferrous six-coordinate species is inactive. Our results indicate that DevS is a gas sensor in vivo rather than a redox sensor and that the stability of its ferrous-oxy complex is enhanced by interdomain interactions.
DevS是负责DevR激活以及随后结核分枝杆菌进入休眠状态的两种传感激酶之一。全长野生型DevS形成稳定的氧亚铁复合物。在K(+)、Na(+)、Mg(2+)和Ca(2+)等阳离子存在的情况下，DevS的自氧化速率极低（半衰期>24小时）。在相对高浓度（100 mM）时，Cu(2+)使自氧化加速超过1500倍。与预期相反，Y171F突变体中铁配位氧与Tyr171之间关键氢键的去除产生了一种自氧化稳定性相当且氧解离速率相似的蛋白质。这与我们早期的发现相关，即Y171F突变体和野生型激酶活性受氧结合的类似调节：即亚铁五配位复合物具有活性，而氧亚铁六配位物种无活性。我们的结果表明，DevS在体内是一种气体传感器而非氧化还原传感器，并且其亚铁 - 氧复合物的稳定性通过结构域间相互作用得到增强。
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