Contributions of methionine to recognition of trimethyllysine in aromatic cage of PHD domains: implications of polarizability, hydrophobicity, and charge on binding.
Contributions of methionine to recognition of trimethyllysine in aromatic cage of PHD domains: implications of polarizability, hydrophobicity, and charge on binding.
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蛋氨酸对 PHD 结构域芳香笼中三甲基赖氨酸识别的贡献：极化性、疏水性和电荷对结合的影响。
DOI：
10.1039/d1sc02175c
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发表时间：
2021-07-01
期刊：
影响因子：
8.4
通讯作者：
Waters ML
中科院分区：
文献类型：
--
作者：
Albanese KI;Waters ML
阅读器蛋白对三甲基赖氨酸 (Kme3) 的识别是基因表达的重要调节因子。该识别事件是由阅读器蛋白中由 2-4 个芳香族残基组成的芳香笼介导的，该芳香笼通过阳离子 - π 相互作用结合 Kme3。一小部分读取蛋白在结合袋中含有甲硫氨酸 (Met) 残基来代替芳香族侧链。最近，硫在分子识别中的独特作用已在许多非共价相互作用中得到证明，包括硫醇、硫醚和亚砜与芳环的相互作用。然而，硫醚与铵离子的相互作用此前尚未被研究，并且 Met 在结合 Kme3 中的作用尚未被探索。在此，我们系统地改变了两种读取蛋白 DIDO1 和 TAF3 以及配体 Kme3 或其中性类似物叔丁基正亮氨酸 (tBuNle) 中的 Met，以确定 Met 在识别阳离子 Kme3 中的作用。我们的研究表明，Met 通过色散力促进结合，对结合 Kme3 和 tBuNle 的贡献大约相等，表明静电相互作用不起作用。在这些研究过程中，我们还发现 DIDO1 通过结合机制的改变表现出与 tBuNle 和 Kme3 等效的结合。三甲基赖氨酸 (Kme3) 阅读器蛋白中的保守蛋氨酸通过分散力而不是离子偶极相互作用或疏水效应相互作用。还发现了 Kme3 与其中性类似物的选择性差异。
Recognition of trimethyllysine (Kme3) by reader proteins is an important regulator of gene expression. This recognition event is mediated by an aromatic cage made up of 2–4 aromatic residues in the reader proteins that bind Kme3 via cation–π interactions. A small subset of reader proteins contain a methionine (Met) residue in place of an aromatic sidechain in the binding pocket. The unique role of sulfur in molecular recognition has been demonstrated in a number of noncovalent interactions recently, including interactions of thiols, thioethers, and sulfoxides with aromatic rings. However, the interaction of a thioether with an ammonium ion has not previously been investigated and the role of Met in binding Kme3 has not yet been explored. Herein, we systematically vary the Met in two reader proteins, DIDO1 and TAF3, and the ligand, Kme3 or its neutral analog tert-butyl norleucine (tBuNle), to determine the role of Met in the recognition of the cationic Kme3. Our studies demonstrate that Met contributes to binding via dispersion forces, with about an equal contribution to binding Kme3 and tBuNle, indicating that electrostatic interactions do not play a role. During the course of these studies, we also discovered that DIDO1 exhibits equivalent binding to tBuNle and Kme3 through a change in the mechanism of binding. A conserved methionine in a trimethyllysine (Kme3) reader protein interacts via dispersion forces rather than ion-dipole interactions or the hydrophobic effect. Differences in selectivity for Kme3 versus its neutral analog were also discovered.
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影响因子：
8.8
作者：
Gatchalian J;Fütterer A;Rothbart SB;Tong Q;Rincon-Arano H;Sánchez de Diego A;Groudine M;Strahl BD;Martínez-A C;van Wely KH;Kutateladze TG
通讯作者：
Kutateladze TG
影响因子：
8
作者：
Gomez-Tamayo, Jose C.;Cordomi, Arnau;Pardo, Leonardo
通讯作者：
Pardo, Leonardo
影响因子：
7.3
作者：
Beno, Brett R.;Yeung, Kap-Sun;Meanwell, Nicholas A.
通讯作者：
Meanwell, Nicholas A.
DOI：
10.1107/s0907444902003359
发表时间：
2002-05-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Hovmöller, S;Zhou, T;Ohlson, T
通讯作者：
Ohlson, T
影响因子：
2.9
作者：
Duewel, H;Daub, E;Honek, JF
通讯作者：
Honek, JF