Investigation of the Importance of Protein 3D Structure for Assessing Conservation of Lysine Acetylation Sites in Protein Homologs.
Investigation of the Importance of Protein 3D Structure for Assessing Conservation of Lysine Acetylation Sites in Protein Homologs.
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DOI：
10.3389/fmicb.2021.805181
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发表时间：
2021
影响因子：
5.2
通讯作者：
Kuhn ML
中科院分区：
文献类型：
--
作者：
Jew KM;Le VTB;Amaral K;Ta A;Nguyen May NM;Law M;Adelstein N;Kuhn ML
乙酰化是一种蛋白质翻译后修饰（PTM），可影响多种细胞过程。在细菌中，已经确定了两种PTM Nε-乙酰化机制：通过乙酰磷酸或乙酰辅酶A的非酶促/化学乙酰化和通过蛋白质乙酰转移酶的酶促乙酰化。先前的研究表明，来自各种细菌的许多蛋白质的Nε-赖氨酸残基的广泛乙酰化通过非酶促乙酰化发生。在大肠杆菌中，已经鉴定了新的Nε-赖氨酸乙酰转移酶（KAT），其酶促乙酰化其他蛋白质，从而扩展了可能由乙酰化调节的蛋白质底物库。因此，我们设计了一项研究，利用蛋白质数据库（PDB）中丰富的结构数据来确定：（1）赖氨酸残基在底物蛋白上的三维位置，这些底物蛋白被E. coliKATs，以及（2）研究这些残基是否在其同源物的三维结构上保守。五E选择先前被鉴定为被YiaC乙酰化并且在PDB中具有3D结构的大肠杆菌KAT底物蛋白用于进一步分析：腺苷酸激酶（Adk）、异柠檬酸脱氢酶（Icd）、过氧化氢酶HPII（KatE）、甲硫氨酰-tRNA甲酰基转移酶（Fmt）和过氧化物应激抗性蛋白（YaaA）。我们系统地比较了这些E.大肠杆菌酶及其同系物;为了准确地确定赖氨酸残基保守性，需要结合灵活的结构比对和目视检查的策略。此外，我们的研究结果显示，当检查线性氨基酸序列相比，三维结构的同源物中的赖氨酸残基保守的结论的差异。
Acetylation is a protein post-translational modification (PTM) that can affect a variety of cellular processes. In bacteria, two PTM Nε-acetylation mechanisms have been identified: non-enzymatic/chemical acetylation via acetyl phosphate or acetyl coenzyme A and enzymatic acetylation via protein acetyltransferases. Prior studies have shown that extensive acetylation of Nε-lysine residues of numerous proteins from a variety of bacteria occurs via non-enzymatic acetylation. In Escherichia coli, new Nε-lysine acetyltransferases (KATs) that enzymatically acetylate other proteins have been identified, thus expanding the repertoire of protein substrates that are potentially regulated by acetylation. Therefore, we designed a study to leverage the wealth of structural data in the Protein Data Bank (PDB) to determine: (1) the 3D location of lysine residues on substrate proteins that are acetylated by E. coli KATs, and (2) investigate whether these residues are conserved on 3D structures of their homologs. Five E. coli KAT substrate proteins that were previously identified as being acetylated by YiaC and had 3D structures in the PDB were selected for further analysis: adenylate kinase (Adk), isocitrate dehydrogenase (Icd), catalase HPII (KatE), methionyl-tRNA formyltransferase (Fmt), and a peroxide stress resistance protein (YaaA). We methodically compared over 350 protein structures of these E. coli enzymes and their homologs; to accurately determine lysine residue conservation requires a strategy that incorporates both flexible structural alignments and visual inspection. Moreover, our results revealed discrepancies in conclusions about lysine residue conservation in homologs when examining linear amino acid sequences compared to 3D structures.
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影响因子：
9.9
作者：
Lanouette, Sylvain;Mongeon, Vanessa;Figeys, Daniel;Couture, Jean-Francois
通讯作者：
Couture, Jean-Francois
DOI：
10.1073/pnas.86.22.8635
发表时间：
1989-11-01
影响因子：
11.1
作者：
HURLEY, JH;THORSNESS, PE;STROUD, RM
通讯作者：
STROUD, RM
影响因子：
10.7
作者：
Klotz, MG;Klassen, GR;Loewen, PC
通讯作者：
Loewen, PC
影响因子：
3.7
作者：
Kuhn ML;Zemaitaitis B;Hu LI;Sahu A;Sorensen D;Minasov G;Lima BP;Scholle M;Mrksich M;Anderson WF;Gibson BW;Schilling B;Wolfe AJ
通讯作者：
Wolfe AJ
影响因子：
3.5
作者：
BORTHWICK, AC;HOLMS, WH;NIMMO, HG
通讯作者：
NIMMO, HG