Coupling Sequence-specific Recognition to DNA Modification
Coupling Sequence-specific Recognition to DNA Modification
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DOI：
10.1074/jbc.m109.015966
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发表时间：
2009-08-21
影响因子：
4.8
通讯作者：
Reich, Norbert O.
中科院分区：
文献类型：
--
作者：
Estabrook, R. August;Nguyen, Trung T.;Reich, Norbert O.
修饰DNA的酶在底物结合和催化方面都面临着巨大的挑战。我们描述了DNA胞嘧啶甲基转移酶M.Hhai与其DNA底物之间的单氢键是如何调节一个类似于28埃远的肽环的定位的。插入环中的色氨酸的停流荧光测量提供了构象重排的实时观察。这些与底物结合和关键是酶的周转相关的长程相互作用将在酶的特异性和这类医学相关酶的药物设计中有广泛的应用。
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 similar to 28 angstrom 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.