Structure of the DNA repair enzyme endonuclease IV and its DNA complex: Double-nucleotide flipping at abasic sites and three-metal-ion catalysis
Structure of the DNA repair enzyme endonuclease IV and its DNA complex: Double-nucleotide flipping at abasic sites and three-metal-ion catalysis
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DOI：
10.1016/s0092-8674(00)81968-6
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发表时间：
1999-08-06
期刊：
影响因子：
64.5
通讯作者：
Tainer, JA
中科院分区：
文献类型：
--
作者：
Hosfield, DJ;Guan, Y;Tainer, JA
核酸内切酶 IV 是保守的脱嘌呤/脱嘧啶 (AP) 核酸内切酶家族的原型，该家族通过切割 AP 位点的 DNA 主链 5' 来启动 DNA 修复合成。核酸内切酶 IV 及其 AP-DNA 复合物在 1.02 和 1.55 埃分辨率下的晶体结构揭示了 alpha(8)beta(8) TIM 桶状折叠如何结合 dsDNA。酶环在脱碱基位点插入侧链，压缩 DNA 主链，使 DNA 弯曲至 90 度，并促进双核苷酸翻转，将螺旋外 AP 位点隔离在酶袋中，排除未损坏的核苷酸。这些结构表明三个 Zn2+ 离子直接参与磷酸二酯键裂解，并提示了这样的假设：AP 核酸内切酶的双核苷酸翻转和急剧弯曲提供了精致的损伤特异性，同时有助于随后的碱基切除修复途径进展。
Endonuclease IV is the archetype for a conserved apurinic/apyrimidinic (AP) endonuclease family that primes DNA repair synthesis by cleaving the DNA backbone 5' of AP sites. The crystal structures of Endonuclease IV and its AP-DNA complex at 1.02 and 1.55 Angstrom resolution reveal how an alpha(8)beta(8) TIM barrel fold can bind dsDNA. Enzyme loops intercalate side chains at the abasic site, compress the DNA backbone, bend the DNA similar to 90 degrees, and promote double-nucleotide flipping to sequester the extrahelical AP site in an enzyme pocket that excludes undamaged nucleotides. These structures suggest three Zn2+ ions directly participate in phosphodiester bond cleavage and prompt hypotheses that double-nucleotide flipping and sharp bending by AP endonucleases provide exquisite damage specificity while aiding subsequent base excision repair pathway progression.