Barzilay G, Mol C D, Robson C N, Walker L J, Cunningham R P, Tainer J A, Hickson I D
Imperial Cancer Research Fund, University of Oxford, John Radcliffe Hospital, UK.
Nat Struct Biol. 1995 Jul;2(7):561-8. doi: 10.1038/nsb0795-561.
All organisms express dedicated repair enzymes for counteracting the cytotoxic and mutagenic potential of apurinic/apyrimidinic (AP) lesions, which would otherwise pose a serious threat to genome integrity. We present the predicted three-dimensional structure of the major human AP site-specific DNA repair endonuclease, HAP1, and show that an aspartate/histidine pair, in conjunction with a metal ion-coordinating glutamate residue, are critical for catalyzing the multiple repair activities of HAP1. We suggest that this catalytic mechanism is conserved in certain reverse transcriptases, but is distinct from the two metal ion-mediated mechanism defined for other hydrolytic nucleases.
所有生物体都表达专门的修复酶，以对抗脱嘌呤/脱嘧啶（AP）损伤的细胞毒性和诱变潜力，否则这些损伤会对基因组完整性构成严重威胁。我们展示了主要的人类AP位点特异性DNA修复内切核酸酶HAP1的预测三维结构，并表明天冬氨酸/组氨酸对与一个金属离子配位谷氨酸残基共同作用，对于催化HAP1的多种修复活性至关重要。我们认为这种催化机制在某些逆转录酶中是保守的，但不同于为其他水解核酸酶定义的双金属离子介导机制。
