Crystal structure of Pelagibacterium halotolerans PE8: New insight into its substrate-binding pattern

Abstract Lysophospholipase_carboxylesterase (LPCE) has highly conserved homologs in many diverse species ranging from bacteria to humans, as well as substantial biological significance and potential therapeutic implications. However, its biological function and catalytic mechanism remain minimally i...

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Autores principales:	Ying-Yi Huo, Suhua Li, Jing Huang, Zhen Rong, Zhao Wang, Zhengyang Li, Rui Ji, Siyun Kuang, Heng-Lin Cui, Jixi Li, Xue-Wei Xu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/76f76113433c400e92b40dff14ab6cdb
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spelling	oai:doaj.org-article:76f76113433c400e92b40dff14ab6cdb2021-12-02T15:05:37ZCrystal structure of Pelagibacterium halotolerans PE8: New insight into its substrate-binding pattern10.1038/s41598-017-04550-72045-2322https://doaj.org/article/76f76113433c400e92b40dff14ab6cdb2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04550-7https://doaj.org/toc/2045-2322Abstract Lysophospholipase_carboxylesterase (LPCE) has highly conserved homologs in many diverse species ranging from bacteria to humans, as well as substantial biological significance and potential therapeutic implications. However, its biological function and catalytic mechanism remain minimally investigated because of the lack of structural information. Here, we report the crystal structure of a bacterial esterase PE8 belonging to the LPCE family. The crystal structure of PE8 was solved with a high resolution of 1.66 Å. Compared with other homologs in the family, significant differences were observed in the amino acid sequence, three-dimensional structure, and substrate-binding pattern. Residue Arg79 undergoes configuration switching when binding to the substrate and forms a unique wall, leading to a relatively closed cavity in the substrate-binding pocket compared with the relatively more open and longer clefts in other homologs. Moreover, the mutant Met122Ala showed much stronger substrate affinity and higher catalytic efficiency because less steric repulsion acted on the substrates. Taken together, these results showed that, in PE8, Arg79 and Met122 play important roles in substrate binding and the binding pocket shaping, respectively. Our study provides new insight into the catalytic mechanism of LPCE, which may facilitate the development of structure-based therapeutics and other biocatalytic applications.Ying-Yi HuoSuhua LiJing HuangZhen RongZhao WangZhengyang LiRui JiSiyun KuangHeng-Lin CuiJixi LiXue-Wei XuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ying-Yi Huo Suhua Li Jing Huang Zhen Rong Zhao Wang Zhengyang Li Rui Ji Siyun Kuang Heng-Lin Cui Jixi Li Xue-Wei Xu Crystal structure of Pelagibacterium halotolerans PE8: New insight into its substrate-binding pattern
description	Abstract Lysophospholipase_carboxylesterase (LPCE) has highly conserved homologs in many diverse species ranging from bacteria to humans, as well as substantial biological significance and potential therapeutic implications. However, its biological function and catalytic mechanism remain minimally investigated because of the lack of structural information. Here, we report the crystal structure of a bacterial esterase PE8 belonging to the LPCE family. The crystal structure of PE8 was solved with a high resolution of 1.66 Å. Compared with other homologs in the family, significant differences were observed in the amino acid sequence, three-dimensional structure, and substrate-binding pattern. Residue Arg79 undergoes configuration switching when binding to the substrate and forms a unique wall, leading to a relatively closed cavity in the substrate-binding pocket compared with the relatively more open and longer clefts in other homologs. Moreover, the mutant Met122Ala showed much stronger substrate affinity and higher catalytic efficiency because less steric repulsion acted on the substrates. Taken together, these results showed that, in PE8, Arg79 and Met122 play important roles in substrate binding and the binding pocket shaping, respectively. Our study provides new insight into the catalytic mechanism of LPCE, which may facilitate the development of structure-based therapeutics and other biocatalytic applications.
format	article
author	Ying-Yi Huo Suhua Li Jing Huang Zhen Rong Zhao Wang Zhengyang Li Rui Ji Siyun Kuang Heng-Lin Cui Jixi Li Xue-Wei Xu
author_facet	Ying-Yi Huo Suhua Li Jing Huang Zhen Rong Zhao Wang Zhengyang Li Rui Ji Siyun Kuang Heng-Lin Cui Jixi Li Xue-Wei Xu
author_sort	Ying-Yi Huo
title	Crystal structure of Pelagibacterium halotolerans PE8: New insight into its substrate-binding pattern
title_short	Crystal structure of Pelagibacterium halotolerans PE8: New insight into its substrate-binding pattern
title_full	Crystal structure of Pelagibacterium halotolerans PE8: New insight into its substrate-binding pattern
title_fullStr	Crystal structure of Pelagibacterium halotolerans PE8: New insight into its substrate-binding pattern
title_full_unstemmed	Crystal structure of Pelagibacterium halotolerans PE8: New insight into its substrate-binding pattern
title_sort	crystal structure of pelagibacterium halotolerans pe8: new insight into its substrate-binding pattern
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/76f76113433c400e92b40dff14ab6cdb
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Crystal structure of Pelagibacterium halotolerans PE8: New insight into its substrate-binding pattern

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