期刊
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
卷 90, 期 3, 页码 670-679出版社
WILEY
DOI: 10.1002/prot.26264
关键词
ATP; biosynthesis; microviridins; peptide macrocyclase; ribosomally synthesized and post-translationally modified peptide
资金
- National Institutes of Health [GM128742, R35GM128742]
- National Institute of General Medical Sciences [AGM-12006]
- National Cancer Institute [ACB12002]
This study reports the structure and biochemical characteristics of AMdnB involved in microviridin biosynthesis from Anabaena sp. PCC 7120, shedding light on the iterative macrocyclization mechanism. AMdnB can introduce multiple macrocyclizations on a precursor peptide in a distributive mode of catalysis. The results provide insight into the general mechanism of iterative enzymes in peptide biosynthetic pathways.
Microviridins, tricyclic peptide natural products originally isolated from cyanobacteria, function as inhibitors of diverse serine-type proteases. Here we report the structure and biochemical characterization of AMdnB, a unique iterative macrocyclase involved in a microviridin biosynthetic pathway from Anabaena sp. PCC 7120. The ATP-dependent cyclase, along with the homologous AMdnC, introduce up to nine macrocyclizations on three distinct core regions of a precursor peptide, AMdnA. The results presented here provide structural and mechanistic insight into the iterative chemistry of AMdnB. In vitro AMdnB-catalyzed cyclization reactions demonstrate the synthesis of the two predicted tricyclic products from a multi-core precursor peptide substrate, consistent with a distributive mode of catalysis. The X-ray structure of AMdnB shows a structural motif common to ATP-grasp cyclases involved in RiPPs biosynthesis. Additionally, comparison with the noniterative MdnB allows insight into the structural basis for the iterative chemistry. Overall, the presented results provide insight into the general mechanism of iterative enzymes in ribosomally synthesized and post-translationally modified peptide biosynthetic pathways.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据