Enzymatic methylation of the amide bond.
Enzymatic methylation of the amide bond.
复制标题
酰胺键的酶促甲基化。
DOI：
10.1016/j.sbi.2020.06.004
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发表时间：
2020
影响因子：
6.8
通讯作者：
Song H
中科院分区：
文献类型：
--
作者：
Song H
重点甲基化酰胺在医学中有应用。肽的化学甲基化是一个挑战。甲基化酰胺的酶已经被表征。其机制依赖于酸/碱化学。酰胺键具有平面性和缺乏化学反应性，是蛋白质结构的核心。酰胺的化学甲基化是已知的，但被认为太苛刻而不能用于生物学。直到去年，数据库中还没有蛋白质结构与酶甲基化酰胺。发现天然大环产物奥曲肽是核糖体合成的，并不像非核糖体肽合成所假设的那样。这是第一个明确的证据表明，酶可以甲基化酰胺键。酶OphMA使用SAM作为辅因子迭代地自我超甲基化其自身的C末端。第二种酶OphP，脯氨酰寡肽酶，从OphMA切割核心肽，并将其环化为omphetin。通过诱变、结构、生化和理论研究阐明了OphMA的分子机制。本文综述了肽N-甲基化酶的研究进展。
HighlightsMethylated amides have application in medicine.Chemical methylation of peptides is challenging.Enzymes which methylated amides have been characterised.The mechanism relies on acid/base chemistry.The amide bond with its planarity and lack of chemical reactivity is at the heart of protein structure. Chemical methylation of amides is known but was considered too harsh to be accessible to biology. Until last year there was no protein structure in the data bank with an enzymatically methylated amide. The discovery that the natural macrocyclic product, omphalotin is ribosomally synthesized, was not as had been assumed by non-ribosomal peptide synthesis. This was the first definitive evidence that an enzyme could methylate the amide bond. The enzyme, OphMA, iteratively self-hypermethylates its own C-terminus using SAM as cofactor. A second enzyme OphP, a prolyl oligopeptidase cleaves the core peptide from OphMA and cyclizes it into omphalotin. The molecular mechanism for OphMA was elucidated by mutagenesis, structural, biochemical and theoretical studies. This review highlights current progress in peptide N-methylating enzymes.
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影响因子：
5.6
作者：
J. Vévodová;R. Graham;E. Raux;H. Schubert;D. Roper;A. Brindley;A. Ian Scott;C. Roessner;N. Stamford;M. Elizabeth Stroupe;E. Getzoff;M. Warren;K. Wilson
通讯作者：
J. Vévodová;R. Graham;E. Raux;H. Schubert;D. Roper;A. Brindley;A. Ian Scott;C. Roessner;N. Stamford;M. Elizabeth Stroupe;E. Getzoff;M. Warren;K. Wilson
DOI：
10.1101/380295
发表时间：
2018-07
期刊：
bioRxiv
影响因子：
--
作者：
A. James;J. Haywood;J. Leroux;K. Ignasiak;Alysha G. Elliott;J. Schmidberger;Mark F. Fisher;S. Nonis;R. Fenske;C. Bond;J. Mylne
通讯作者：
A. James;J. Haywood;J. Leroux;K. Ignasiak;Alysha G. Elliott;J. Schmidberger;Mark F. Fisher;S. Nonis;R. Fenske;C. Bond;J. Mylne
影响因子：
4
作者：
Ongpipattanakul C;Nair SK
通讯作者：
Nair SK
DOI：
10.1016/s0021-9258(17)42019-9
发表时间：
1994-01
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
J. Dittmann;R. Wenger;H. Kleinkauf;Alfons Lawen
通讯作者：
J. Dittmann;R. Wenger;H. Kleinkauf;Alfons Lawen
影响因子：
16.6
作者：
Ramm, Sascha;Krawczyk, Bartlomiej;Suessmuth, Roderich D.
通讯作者：
Suessmuth, Roderich D.