Structural Studies of DNA repair proteins

DNA修复蛋白的结构研究

• 批准号: 6487426
• 负责人: Brandt F Eichman
• 金额: $ 3.83万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6487426
• 关键词: DNA; DNA repair; N glycosidase; X ray crystallography; affinity chromatography; bacterial proteins; crystallization; enzyme activity; enzyme model; enzyme substrate complex; fungal proteins; intermolecular interaction; microorganism culture; model design /development; molecular site; postdoctoral investigator; protein folding; protein purification; protein structure function; site directed mutagenesis; structural biology

DESCRIPTION: (provided by applicant) Base excision repair is an important process to understand because damaged DNA bases are known to produce mutations, which can cause hereditary diseases and cancer. A family of alkylation-specific DNA glycosylases is responsible for locating and removing several types of modified bases. Some 3-methyladenine (3-MeA) glycosylases are specific for a certain type of alkylated base, whereas others have a broad specificity. Moreover, these different classes of 3-MeA glycosylases are represented in the large family of helix-hairpin-helix (HhH) glycosylases. The goal of the proposed studies is to understand the structural reason for differences in the substrate specificities of 3-MeA DNA glycosylases that share common folds, and to address the mechanism by which these enzymes locate and remove damaged bases from DNA. To address these questions, the crystal structures of three HhH 3-MeA DNA glycosylases representing two extremes in substrate specificity will be determined in the presence and absence of DNA substrates. H. pylori MagIII is highly specific for 3-MeA residues, while S. cerevisiae MAO and S. pombe MagI have a broad specificity. Crystals of MagIII protein and of MagI/DNA complexes have already been obtained.

说明：（由申请人提供）基底切除修复是重要的