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Bacterial DNA Methyltransferases

Bacterial DNA Methyltransferases
细菌 DNA 甲基转移酶
批准号:
9983125
负责人:
Norbert Reich
金额:
$34.17万
依托单位国家:
美国
项目类别:
Continuing Grant
财政年份:
2000
资助国家:
美国
项目状态:
已结题
起止时间:
2000-04-01 至 2004-01-31

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中文摘要
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英文摘要
9983125ReichEnzymes that alter the structure of DNA perform functions that are essential for life. DNA methyltransferases expand the information content of DNA by modifying specific adenines and cytosines. DNA methylation is the most common form of epigenetic control of gene expression and occurs in organisms ranging from bacteria to man. This is an essential modification whose mechanism is not completely understood. This project addresses this topic using bacterial enzymes in an attempt to understand the molecular basis of sequence-specific DNA modification. DNA methylases bend the DNA and flip out their target bases prior to catalysis. This project builds on recent discoveries funded by NSF and conducted in this PI's laboratory, that allow the tracking of both DNA bending and base flipping in real time. This research area, the study of conformational mechanisms of DNA modifying enzymes, is only feasible through the use of several kinetic and spectroscopic methods pioneered by the PI and in conjunction with collaborators. Understanding the underlying mechanisms of such conformational changes is critical if we are to appreciate how such enzymes discriminate among DNA sequences, and carry out their particular chemistries. Most importantly, other methods such as x-ray crystallography do not provide the necessary quantitative and functional insights since they cannot provide dynamic information. This information is clearly important to gain an understanding of conformational transitions to enzyme specificity. The insights provided by this research should have implications for understanding the mechanism of action of other enzymes such as those involved in DNA repair since many of them also appear to use similar conformational mechanisms, as revealed by other investigators using methods similar to those pioneered here.
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Mechanistic investigation of processive and distributive DNA modification
Mechanistic investigation of protein translocation on DNA
Structure Function Analysis of Bacterial DNA Methyltransferase
Acquisition of an Electrospray Mass Spectrometer
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