Bailey Lucas J, McCoy Jason G, Phillips George N, Fox Brian G
Department of Biochemistry, University of Wisconsin, 433 Babcock Drive, Madison, WI 53706-1544, USA.
Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19194-8. doi: 10.1073/pnas.0807948105. Epub 2008 Nov 25.
Carboxylate-bridged diiron hydroxylases are multicomponent enzyme complexes responsible for the catabolism of a wide range of hydrocarbons and as such have drawn attention for their mechanism of action and potential uses in bioremediation and enzymatic synthesis. These enzyme complexes use a small molecular weight effector protein to modulate the function of the hydroxylase. However, the origin of these functional changes is poorly understood. Here, we report the structures of the biologically relevant effector protein-hydroxylase complex of toluene 4-monooxygenase in 2 redox states. The structures reveal a number of coordinated changes that occur up to 25 A from the active site and poise the diiron center for catalysis. The results provide a structural basis for the changes observed in a number of the measurable properties associated with effector protein binding. This description provides insight into the functional role of effector protein binding in all carboxylate-bridged diiron hydroxylases.
羧酸盐桥连二铁羟化酶是多组分酶复合物,负责多种碳氢化合物的分解代谢,因此其作用机制以及在生物修复和酶促合成中的潜在用途备受关注。这些酶复合物利用一种小分子量效应蛋白来调节羟化酶的功能。然而,这些功能变化的起源却知之甚少。在此,我们报道了处于两种氧化还原状态的甲苯4-单加氧酶的生物学相关效应蛋白-羟化酶复合物的结构。这些结构揭示了在距活性位点达25埃处发生的一系列协同变化,并使二铁中心处于催化状态。这些结果为与效应蛋白结合相关的一些可测量性质中观察到的变化提供了结构基础。这一描述为效应蛋白结合在所有羧酸盐桥连二铁羟化酶中的功能作用提供了深入见解。