Modular catalytic activity of nonribosomal peptide synthetases depends on the dynamic interaction between adenylation and condensation domains

被引:1
作者
Peng, Ye-Jun [1 ,5 ]
Chen, Yuxing [4 ]
Zhou, Cong-Zhao [4 ]
Miao, Wei [2 ,3 ]
Jiang, Yong-Liang [4 ]
Zeng, Xiaoli [1 ,2 ]
Zhang, Cheng-Cai [1 ,2 ,3 ]
机构
[1] Chinese Acad Sci, Inst Hydrobiol, Key Lab Algal Biol, Wuhan 430072, Hubei, Peoples R China
[2] Chinese Acad Sci, Key Lab Lake & Watershed Sci Water Secur, Nanjing 210008, Peoples R China
[3] Hubei Hongshan Lab, Wuhan 430070, Peoples R China
[4] Univ Sci & Technol China, Sch Life Sci, Div Life Sci & Med, Hefei 230026, Peoples R China
[5] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
基金
国家重点研发计划;
关键词
CONFORMATIONAL-CHANGES; CRYSTAL-STRUCTURE; PROTEIN; CARRIER; BIOSYNTHESIS; MECHANISM; TOXINS; THIOESTERASE; POLYKETIDE; CYCLE;
D O I
10.1016/j.str.2024.01.010
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nonribosomal peptide synthetases (NRPSs) are large multidomain enzymes for the synthesis of a variety of bioactive peptides in a modular and pipelined fashion. Here, we investigated how the condensation (C) domain and the adenylation (A) domain cooperate with each other for the efficient catalytic activity in microcystin NRPS modules. We solved two crystal structures of the microcystin NRPS modules, representing two different conformations in the NRPS catalytic cycle. Our data reveal that the dynamic interaction between the C and the A domains in these modules is mediated by the conserved "RXGR"motif, and this interaction is important for the adenylation activity. Furthermore, the "RXGR"motif-mediated dynamic interaction and its functional regulation are prevalent in different NRPSs modules possessing both the A and the C domains. This study provides new insights into the catalytic mechanism of NRPSs and their engineering strategy for synthetic peptides with different structures and properties.
引用
收藏
页码:440 / 452.e4
页数:18
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