Cascading proton transfers are a hallmark of the catalytic mechanism of SAM-dependent methyltransferases.

IF 3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Li Na Zhao, Philipp Kaldis
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引用次数: 0

Abstract

The S-adenosyl methionine (SAM)-dependent methyltransferases attach a methyl group to the deprotonated methyl lysine using SAM as a donor. An intriguing, yet unanswered, question is how the deprotonation takes place. PRDM9 with well-defined enzyme activity is a good representative of the methyltransferase family to study the deprotonation and subsequently the methyl transfer. Our study has found that the pKa of Tyr357 is low enough to make it an ideal candidate for proton abstraction from the methyl lysine. The partially deprontonated Tyr357 is able to change its H-bond pattern thus bridging two proton tunneling states and providing a cascading proton transfer. We have uncovered a new catalytic mechanism for the deprotonation of the methyl lysine in methyltransferases.

级联质子转移是依赖于 SAM 的甲基转移酶催化机制的标志。
依赖于 S-腺苷蛋氨酸(SAM)的甲基转移酶以 SAM 为供体,将一个甲基连接到去质子化的甲基赖氨酸上。一个有趣但尚未解答的问题是,去质子化是如何进行的。具有明确酶活性的 PRDM9 是甲基转移酶家族中研究去质子化和随后甲基转移的一个很好的代表。我们的研究发现,Tyr357 的 pKa 很低,足以使其成为从甲基赖氨酸中抽取质子的理想候选物。部分去锶的 Tyr357 能够改变其 H 键模式,从而连接两个质子隧道态,实现质子的级联转移。我们发现了甲基转移酶中甲基赖氨酸去质子化的新催化机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
FEBS Letters
FEBS Letters 生物-生化与分子生物学
CiteScore
6.60
自引率
2.90%
发文量
303
审稿时长
1 months
期刊介绍: FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.
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