The crystal structure of the human DNA repair endonuclease HAP1 suggests the recognition of extra-helical deoxyribose at DNA abasic sites
The crystal structure of the human DNA repair endonuclease HAP1 suggests the recognition of extra-helical deoxyribose at DNA abasic sites
复制标题
DOI：
10.1093/emboj/16.21.6548
复制
发表时间：
1997-11-03
期刊：
影响因子：
11.4
通讯作者：
Freemont, PS
中科院分区：
文献类型：
--
作者：
Gorman, MA;Morera, S;Freemont, PS
主要人类无嘌呤/无嘧啶核酸内切酶 (HAP1) 的结构已在 2.2 埃分辨率下得到解析。该酶由两个拓扑相似的对称相关结构域组成，与牛 DNase I 及其大肠杆菌同源核酸外切酶 III (EXOIII) 具有显着的结构相似性，这些酶的结构比较揭示了 HAP1 和 EXOIII 特异的三个环区域，这些环区域显然在 DNA 无碱基位点 (AP) 识别和切割中起作用，因为缺乏这些环的 DNase I 相应地缺乏 AP 位点特异性，HAP1 结构此外还提出了一种AP位点结合机制，涉及识别螺旋外构象中的脱氧核糖部分，而不是与AP位点相对的“翻转”碱基。
The structure of the major human apurinic/apyrimidinic endonuclease (HAP1) has been solved at 2.2 Angstrom resolution. The enzyme consists of two symmetrically related domains of similar topology and has significant structural similarity to both bovine DNase I and its Escherichia coli homologue exonuclease III (EXOIII), A structural comparison of these enzymes reveals three loop regions specific to HAP1 and EXOIII, These loop regions apparently act in DNA abasic site (AP) recognition and cleavage since DNase I, which lacks these loops, correspondingly lacks AP site specificity, The HAP1 structure furthermore suggests a mechanism for AP site binding which involves the recognition of the deoxyribose moiety in an extrahelical conformation, rather than a 'flipped-out' base opposite the AP site.