将序列特异性识别与DNA修饰相结合。
Coupling sequence-specific recognition to DNA modification.
作者信息
Estabrook R August, Nguyen Trung T, Fera Nickolas, Reich Norbert O
机构信息
Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106, USA.
出版信息
J Biol Chem. 2009 Aug 21;284(34):22690-6. doi: 10.1074/jbc.M109.015966. Epub 2009 Jun 4.
Abstract
Enzymes that modify DNA are faced with significant challenges in specificity for both substrate binding and catalysis. We describe how single hydrogen bonds between M.HhaI, a DNA cytosine methyltransferase, and its DNA substrate regulate the positioning of a peptide loop which is approximately 28 A away. Stopped-flow fluorescence measurements of a tryptophan inserted into the loop provide real-time observations of conformational rearrangements. These long-range interactions that correlate with substrate binding and critically, enzyme turnover, will have broad application to enzyme specificity and drug design for this medically relevant class of enzymes.
摘要
修饰DNA的酶在底物结合和催化的特异性方面面临重大挑战。我们描述了DNA胞嘧啶甲基转移酶M.HhaI与其DNA底物之间的单个氢键如何调节距离约28埃的肽环的定位。对插入该环中的色氨酸进行的停流荧光测量提供了构象重排的实时观察结果。这些与底物结合相关的远程相互作用，以及至关重要的酶周转，将在医学相关的这类酶的酶特异性和药物设计中具有广泛的应用。
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