化损坏的DNA的切割修复的结构基础
J Labahn1, O D Schärer, A Long
1Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology, Boston, Massachusetts02115, USA.
Cell
|July 26, 1996
概括
DNA修复蛋白AlkA通过独特的芳香口袋识别受损的DNA基,揭示了基切割修复机制的洞察力. 这项研究强调了AlkAA如何发挥作用.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 基切除DNA修复对于消除化导致的DNA损伤至关重要.
- 像AlkA (大肠杆菌3-甲基氨酸-DNA糖酶II) 这样的蛋白质准特定的DNA添加物,但具有不同的识别能力.
- 了解DNA修复酶特异性的结构基础对于理解基因组稳定性至关重要.
研究的目的:
- 阐明单功能DNA糖酶AlkA.通过DNA损伤识别的结构和机制基础.
- 研究特定氨基酸残留物和活性部位特征在AlkA的催化活性和基质特异性中的作用.
- 将AlkA的结构特征与其他DNA修复酶 (如内核酶III) 进行比较.
主要方法:
- 使用X射线晶体学来确定AlkA.的1.8 Å晶体结构.
- 生物化学试验被用来评估AlkA.的催化活性和基质结合特异性.
- 用局部定向突变发生法来研究关键残留物,如酸在酶功能中的作用.
主要成果:
- 晶体结构揭示了AlkA内部的大型,富含芳香的疏水裂,这对于结合DNA基来说至关重要.
- 裂内的一种必不可少的酸残留物被确定为催化剂和抑制剂结合特异性的关键.
- 阿尔克A与内核酶III的结构相似性表明,在基切割修复中保留了机制.
结论:
- AlkA通过其芳香活性位点裂内的pi-捐赠者/受体相互作用来识别缺乏电子的甲基.
- 对AlkA的结构洞察力为理解DNA化损伤修复提供了基础.
- AlkA和内核酶III之间的基本相似性表明,在不同的DNA修复蛋白中存在相关的基切除机制.
相关概念视频
Nucleotide Excision Repair
Overview
Overview of DNA Repair
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
Base Excision Repair
One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...
The first step of...
Nucleotide Excision Repair
Overview
Base Excision Repair
One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...
The first step of...
Nucleotide Excision Repair
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...


