Bifunctional quorum-quenching and antibiotic-acylase MacQ forms a 170-kDa capsule-shaped molecule containing spacer polypeptides

Abstract Understanding the molecular mechanisms of bacterial antibiotic resistance will help prepare against further emergence of multi-drug resistant strains. MacQ is an enzyme responsible for the multi-drug resistance of Acidovorax sp. strain MR-S7. MacQ has acylase activity against both N-acylhom...

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Autores principales:	Yoshiaki Yasutake, Hiroyuki Kusada, Teppei Ebuchi, Satoshi Hanada, Yoichi Kamagata, Tomohiro Tamura, Nobutada Kimura
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ee7db31f52ac4cc1bc23bed46f61ca80
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spelling	oai:doaj.org-article:ee7db31f52ac4cc1bc23bed46f61ca802021-12-02T15:05:45ZBifunctional quorum-quenching and antibiotic-acylase MacQ forms a 170-kDa capsule-shaped molecule containing spacer polypeptides10.1038/s41598-017-09399-42045-2322https://doaj.org/article/ee7db31f52ac4cc1bc23bed46f61ca802017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09399-4https://doaj.org/toc/2045-2322Abstract Understanding the molecular mechanisms of bacterial antibiotic resistance will help prepare against further emergence of multi-drug resistant strains. MacQ is an enzyme responsible for the multi-drug resistance of Acidovorax sp. strain MR-S7. MacQ has acylase activity against both N-acylhomoserine lactones (AHLs), a class of signalling compounds involved in quorum sensing, and β-lactam antibiotics. Thus, MacQ is crucial as a quencher of quorum sensing as well as in conferring antibiotic resistance in Acidovorax. Here, we report the X-ray structures of MacQ in ligand-free and reaction product complexes. MacQ forms a 170-kDa capsule-shaped molecule via face-to-face interaction with two heterodimers consisting of an α-chain and a β-chain, generated by the self-cleaving activity of a precursor polypeptide. The electron density of the spacer polypeptide in the hollow of the molecule revealed the close orientation of the peptide-bond atoms of Val20SP-Gly21SP to the active-site, implying a role of the residues in substrate binding. In mutational analyses, uncleaved MacQ retained degradation activity against both AHLs and penicillin G. These results provide novel insights into the mechanism of self-cleaving maturation and enzymatic function of N-terminal nucleophile hydrolases.Yoshiaki YasutakeHiroyuki KusadaTeppei EbuchiSatoshi HanadaYoichi KamagataTomohiro TamuraNobutada KimuraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yoshiaki Yasutake Hiroyuki Kusada Teppei Ebuchi Satoshi Hanada Yoichi Kamagata Tomohiro Tamura Nobutada Kimura Bifunctional quorum-quenching and antibiotic-acylase MacQ forms a 170-kDa capsule-shaped molecule containing spacer polypeptides
description	Abstract Understanding the molecular mechanisms of bacterial antibiotic resistance will help prepare against further emergence of multi-drug resistant strains. MacQ is an enzyme responsible for the multi-drug resistance of Acidovorax sp. strain MR-S7. MacQ has acylase activity against both N-acylhomoserine lactones (AHLs), a class of signalling compounds involved in quorum sensing, and β-lactam antibiotics. Thus, MacQ is crucial as a quencher of quorum sensing as well as in conferring antibiotic resistance in Acidovorax. Here, we report the X-ray structures of MacQ in ligand-free and reaction product complexes. MacQ forms a 170-kDa capsule-shaped molecule via face-to-face interaction with two heterodimers consisting of an α-chain and a β-chain, generated by the self-cleaving activity of a precursor polypeptide. The electron density of the spacer polypeptide in the hollow of the molecule revealed the close orientation of the peptide-bond atoms of Val20SP-Gly21SP to the active-site, implying a role of the residues in substrate binding. In mutational analyses, uncleaved MacQ retained degradation activity against both AHLs and penicillin G. These results provide novel insights into the mechanism of self-cleaving maturation and enzymatic function of N-terminal nucleophile hydrolases.
format	article
author	Yoshiaki Yasutake Hiroyuki Kusada Teppei Ebuchi Satoshi Hanada Yoichi Kamagata Tomohiro Tamura Nobutada Kimura
author_facet	Yoshiaki Yasutake Hiroyuki Kusada Teppei Ebuchi Satoshi Hanada Yoichi Kamagata Tomohiro Tamura Nobutada Kimura
author_sort	Yoshiaki Yasutake
title	Bifunctional quorum-quenching and antibiotic-acylase MacQ forms a 170-kDa capsule-shaped molecule containing spacer polypeptides
title_short	Bifunctional quorum-quenching and antibiotic-acylase MacQ forms a 170-kDa capsule-shaped molecule containing spacer polypeptides
title_full	Bifunctional quorum-quenching and antibiotic-acylase MacQ forms a 170-kDa capsule-shaped molecule containing spacer polypeptides
title_fullStr	Bifunctional quorum-quenching and antibiotic-acylase MacQ forms a 170-kDa capsule-shaped molecule containing spacer polypeptides
title_full_unstemmed	Bifunctional quorum-quenching and antibiotic-acylase MacQ forms a 170-kDa capsule-shaped molecule containing spacer polypeptides
title_sort	bifunctional quorum-quenching and antibiotic-acylase macq forms a 170-kda capsule-shaped molecule containing spacer polypeptides
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/ee7db31f52ac4cc1bc23bed46f61ca80
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_version_	1718388742584008704

Bifunctional quorum-quenching and antibiotic-acylase MacQ forms a 170-kDa capsule-shaped molecule containing spacer polypeptides

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