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Autori principali: Wang, Wenxue, Wang, Peng, Ma, Chuanteng, Li, Kang, Wang, Zian, Liu, Yuting, Wang, Lu, Zhang, Guojian, Che, Qian, Zhu, Tianjiao, Zhang, Yuzhong, Li, Dehai
Natura: Artículo científico
Lingua:en
Pubblicazione: Nature communications 2025
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Accesso online:https://pubmed.ncbi.nlm.nih.gov/39747040/
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author Wang, Wenxue
Wang, Peng
Ma, Chuanteng
Li, Kang
Wang, Zian
Liu, Yuting
Wang, Lu
Zhang, Guojian
Che, Qian
Zhu, Tianjiao
Zhang, Yuzhong
Li, Dehai
author_facet Wang, Wenxue
Wang, Peng
Ma, Chuanteng
Li, Kang
Wang, Zian
Liu, Yuting
Wang, Lu
Zhang, Guojian
Che, Qian
Zhu, Tianjiao
Zhang, Yuzhong
Li, Dehai
Wang, Wenxue
Wang, Peng
Ma, Chuanteng
Li, Kang
Wang, Zian
Liu, Yuting
Wang, Lu
Zhang, Guojian
Che, Qian
Zhu, Tianjiao
Zhang, Yuzhong
Li, Dehai
collection PubMed - marine biology
contents Characterization and structural analysis of a versatile aromatic prenyltransferase for imidazole-containing diketopiperazines. Wang, Wenxue Wang, Peng Ma, Chuanteng Li, Kang Wang, Zian Liu, Yuting Wang, Lu Zhang, Guojian Che, Qian Zhu, Tianjiao Zhang, Yuzhong Li, Dehai Imidazoles Dimethylallyltranstransferase Cryoelectron Microscopy Diketopiperazines Prenylation Substrate Specificity Mutation Bacterial Proteins Models, Molecular Streptomyces Prenylation modifications of natural products play essential roles in chemical diversity and bioactivities, but imidazole modification prenyltransferases are not well investigated. Here, we discover a dimethylallyl tryptophan synthase family prenyltransferase, AuraA, that catalyzes the rare dimethylallylation on the imidazole moiety in the biosynthesis of aurantiamine. Biochemical assays validate that AuraA could accept both cyclo-(L-Val-L-His) and cyclo-(L-Val-DH-His) as substrates, while the prenylation modes are completely different, yielding C2-regular and C5-reverse products, respectively. Cryo-electron microscopy analysis of AuraA and its two ternary complex structures reveal two distinct modes for receptor binding, demonstrating a tolerance for altered orientations of highly similar receptors. The mutation experiments further demonstrate the promiscuity of AuraA towards imidazole-C-dimethylallylation. In this work, we also characterize a case of AuraA mutant-catalyzed dimethylallylation of imidazole moiety, offering available structural insights into the utilization and engineering of dimethylallyl tryptophan synthase family prenyltransferases.
format Artículo científico
id pubmed_39747040
institution PubMed
language en
publishDate 2025
publisher Nature communications
record_format pubmed
spellingShingle Characterization and structural analysis of a versatile aromatic prenyltransferase for imidazole-containing diketopiperazines.
Wang, Wenxue
Wang, Peng
Ma, Chuanteng
Li, Kang
Wang, Zian
Liu, Yuting
Wang, Lu
Zhang, Guojian
Che, Qian
Zhu, Tianjiao
Zhang, Yuzhong
Li, Dehai
Imidazoles
Dimethylallyltranstransferase
Cryoelectron Microscopy
Diketopiperazines
Prenylation
Substrate Specificity
Mutation
Bacterial Proteins
Models, Molecular
Streptomyces
Characterization and structural analysis of a versatile aromatic prenyltransferase for imidazole-containing diketopiperazines. Wang, Wenxue Wang, Peng Ma, Chuanteng Li, Kang Wang, Zian Liu, Yuting Wang, Lu Zhang, Guojian Che, Qian Zhu, Tianjiao Zhang, Yuzhong Li, Dehai Imidazoles Dimethylallyltranstransferase Cryoelectron Microscopy Diketopiperazines Prenylation Substrate Specificity Mutation Bacterial Proteins Models, Molecular Streptomyces Prenylation modifications of natural products play essential roles in chemical diversity and bioactivities, but imidazole modification prenyltransferases are not well investigated. Here, we discover a dimethylallyl tryptophan synthase family prenyltransferase, AuraA, that catalyzes the rare dimethylallylation on the imidazole moiety in the biosynthesis of aurantiamine. Biochemical assays validate that AuraA could accept both cyclo-(L-Val-L-His) and cyclo-(L-Val-DH-His) as substrates, while the prenylation modes are completely different, yielding C2-regular and C5-reverse products, respectively. Cryo-electron microscopy analysis of AuraA and its two ternary complex structures reveal two distinct modes for receptor binding, demonstrating a tolerance for altered orientations of highly similar receptors. The mutation experiments further demonstrate the promiscuity of AuraA towards imidazole-C-dimethylallylation. In this work, we also characterize a case of AuraA mutant-catalyzed dimethylallylation of imidazole moiety, offering available structural insights into the utilization and engineering of dimethylallyl tryptophan synthase family prenyltransferases.
title Characterization and structural analysis of a versatile aromatic prenyltransferase for imidazole-containing diketopiperazines.
topic Imidazoles
Dimethylallyltranstransferase
Cryoelectron Microscopy
Diketopiperazines
Prenylation
Substrate Specificity
Mutation
Bacterial Proteins
Models, Molecular
Streptomyces
url https://pubmed.ncbi.nlm.nih.gov/39747040/