新加坡国立大学Morinaka, Brandon I.团队报道了具有独特的结构褶皱，并催化环烷形成和β-羟基化的融合自由基SAM和αKG-HExxH结构域蛋白。相关研究成果发表在2024年9月18日出版的《自然—化学》。

自然界中金属蛋白中两个反复出现的结合基序，是自由基SAM酶中的CxxxCxxC基序和锌、α-酮戊二酸和非血红素铁酶中发现的2- hs -1-羧酸基序。

该文中，研究人员展示了这两个结构域在单个翻译后修饰酶中的融合，该修饰酶包含一个N-末端自由基S-腺苷甲硫氨酸结构域，该结构域与一个C-末端2-His-1-羧酸盐（HExxH）结构域融合。自由基SAM结构域催化三残基环烷的形成，是三肽（三肽是一类核糖体合成和翻译后修饰的肽）的标志性修饰。

HExxH结构域是锌金属蛋白酶的一个决定性特征。然而，该研究种含HExxH基序的结构域催化β-羟基化，是一种α-酮戊二酸非血红素铁酶。研究人员在2.8处确定了这种HExxH蛋白的晶体结构，揭示了一个独特的结构折叠，从而扩展了α-酮戊二酸非血红素铁酶家族，并将其命名为αKG HExxH。

αKG HExxH蛋白代表了一个独特的核糖体合成和翻译后修饰的肽修饰酶家族，可以为基因组挖掘、合成生物学和酶学提供机会。

附：英文原文

Title: Fused radical SAM and αKG-HExxH domain proteins contain a distinct structural fold and catalyse cyclophane formation and β-hydroxylation

Author: Morishita, Yohei, Ma, Suze, De La Mora, Eugenio, Li, He, Chen, Heng, Ji, Xinjian, Usclat, Anthony, Amara, Patricia, Sugiyama, Ryosuke, Tooh, Yi Wei, Gunawan, Gregory, Prard, Julien, Nicolet, Yvain, Zhang, Qi, Morinaka, Brandon I.

Issue&Volume: 2024-09-18

Abstract: Two of nature’s recurring binding motifs in metalloproteins are the CxxxCxxC motif in radical SAM enzymes and the 2-His-1-carboxylate motif found both in zincins and α-ketoglutarate and non-haem iron enzymes. Here we show the confluence of these two domains in a single post-translational modifying enzyme containing an N-terminal radical S-adenosylmethionine domain fused to a C-terminal 2-His-1-carboxylate (HExxH) domain. The radical SAM domain catalyses three-residue cyclophane formation and is the signature modification of triceptides, a class of ribosomally synthesized and post-translationally modified peptides. The HExxH domain is a defining feature of zinc metalloproteases. Yet the HExxH motif-containing domain studied here catalyses β-hydroxylation and is an α-ketoglutarate non-haem iron enzyme. We determined the crystal structure for this HExxH protein at 2.8, unveiling a distinct structural fold, thus expanding the family of α-ketoglutarate non-haem iron enzymes with a class that we propose to name αKG-HExxH. αKG-HExxH proteins represent a unique family of ribosomally synthesized and post-translationally modified peptide modifying enzymes that can furnish opportunities for genome mining, synthetic biology and enzymology.

DOI: 10.1038/s41557-024-01596-9

Source: https://www.nature.com/articles/s41557-024-01596-9