Rothwell D G, Barzilay G, Gorman M, Morera S, Freemont P, Hickson I D
Imperial Cancer Research Fund Laboratories, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, UK.
Oncol Res. 1997;9(6-7):275-80.
The HAP1/Ref-1 (hereafter referred to as HAP1) protein is a nuclear enzyme that apparently performs two distinct roles in the cellular defense against oxidative stress. One well-established role is in the repair of a variety of lesions induced in DNA either by spontaneous hydrolysis or by reactive oxygen species (ROS). This function has been characterized in great detail and the roles played by individual active site amino acid residues have been defined. The second role, which was identified only relatively recently and is still not characterized in detail, is to regulate the DNA binding activity of a group of nuclear factors. This second role proceeds via the modification of the oxidation/reduction (redox) state of a cysteine residue in the target protein, although the mechanism by which this is achieved remains to be elucidated. In this article, we shall review the latest knowledge on the relationship between structure and the dual functions of HAP1, and we will seek to explain in detail the roles played by several individual amino acid residues in the catalytic function of the HAP1 protein.
HAP1/Ref-1蛋白（以下简称HAP1）是一种核酶，在细胞抵御氧化应激过程中显然发挥着两种不同的作用。一个已被充分证实的作用是修复由自发水解或活性氧（ROS）诱导产生的多种DNA损伤。这一功能已得到详细的表征，并且已明确了各个活性位点氨基酸残基所起的作用。第二个作用是调节一组核因子的DNA结合活性，这一作用相对较新才被发现，目前仍未得到详细表征。这第二个作用是通过改变靶蛋白中半胱氨酸残基的氧化/还原（氧化还原）状态来实现的，不过其实现机制仍有待阐明。在本文中，我们将综述关于HAP1结构与双重功能之间关系的最新知识，并详细解释几个单个氨基酸残基在HAP1蛋白催化功能中所起的作用。
