Insight into the structural stability of wild-type and histidine mutants in Pin1 by experimental and computational methods

Abstract Pin1, a polypeptide proline isomerase parvulin, plays a key role in Alzheimer’s disease (AD), common tumors and cancers. Two conservative histidine residues, His59 and His157, are important for maintaining the stability of the PPIase domain. Hence multiple spectral and computational techniq...

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Autores principales:	Wang Wang, Lei Xi, Xiuhong Xiong, Xue Li, Qingyan Zhang, Wentao Yang, Linfang Du
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7b16f9908d9640838edcda5fed0c2dd7
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spelling	oai:doaj.org-article:7b16f9908d9640838edcda5fed0c2dd72021-12-02T15:09:14ZInsight into the structural stability of wild-type and histidine mutants in Pin1 by experimental and computational methods10.1038/s41598-019-44926-52045-2322https://doaj.org/article/7b16f9908d9640838edcda5fed0c2dd72019-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-44926-5https://doaj.org/toc/2045-2322Abstract Pin1, a polypeptide proline isomerase parvulin, plays a key role in Alzheimer’s disease (AD), common tumors and cancers. Two conservative histidine residues, His59 and His157, are important for maintaining the stability of the PPIase domain. Hence multiple spectral and computational techniques were performed to investigate the potential mechanism of two histidine residues. Thermal denaturation indicated that both residues His59 and His157 are not sensitive to the lower temperatures, while residue His59 is more sensitive to the higher temperatures than residue His157. Acidic denaturation suggested that influences of both residues His59 and His157 to acidic stability were the difference from Pin1-WT. ANS and RLS spectra hinted that there was no significant effect on hydrophobic change and aggregation by histidine mutations. The GndHCl-induced denaturation implied that residues His59 and His157 contributed the most to the chemical stability. MD simulations revealed that residues His59 and His157 mutations resulted in that the hydrogen bond network of the dual histidine motif was destroyed wholly. In summary, these histidine residues play an important role in maintaining the structural stability of the PPIase domain.Wang WangLei XiXiuhong XiongXue LiQingyan ZhangWentao YangLinfang DuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-14 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wang Wang Lei Xi Xiuhong Xiong Xue Li Qingyan Zhang Wentao Yang Linfang Du Insight into the structural stability of wild-type and histidine mutants in Pin1 by experimental and computational methods
description	Abstract Pin1, a polypeptide proline isomerase parvulin, plays a key role in Alzheimer’s disease (AD), common tumors and cancers. Two conservative histidine residues, His59 and His157, are important for maintaining the stability of the PPIase domain. Hence multiple spectral and computational techniques were performed to investigate the potential mechanism of two histidine residues. Thermal denaturation indicated that both residues His59 and His157 are not sensitive to the lower temperatures, while residue His59 is more sensitive to the higher temperatures than residue His157. Acidic denaturation suggested that influences of both residues His59 and His157 to acidic stability were the difference from Pin1-WT. ANS and RLS spectra hinted that there was no significant effect on hydrophobic change and aggregation by histidine mutations. The GndHCl-induced denaturation implied that residues His59 and His157 contributed the most to the chemical stability. MD simulations revealed that residues His59 and His157 mutations resulted in that the hydrogen bond network of the dual histidine motif was destroyed wholly. In summary, these histidine residues play an important role in maintaining the structural stability of the PPIase domain.
format	article
author	Wang Wang Lei Xi Xiuhong Xiong Xue Li Qingyan Zhang Wentao Yang Linfang Du
author_facet	Wang Wang Lei Xi Xiuhong Xiong Xue Li Qingyan Zhang Wentao Yang Linfang Du
author_sort	Wang Wang
title	Insight into the structural stability of wild-type and histidine mutants in Pin1 by experimental and computational methods
title_short	Insight into the structural stability of wild-type and histidine mutants in Pin1 by experimental and computational methods
title_full	Insight into the structural stability of wild-type and histidine mutants in Pin1 by experimental and computational methods
title_fullStr	Insight into the structural stability of wild-type and histidine mutants in Pin1 by experimental and computational methods
title_full_unstemmed	Insight into the structural stability of wild-type and histidine mutants in Pin1 by experimental and computational methods
title_sort	insight into the structural stability of wild-type and histidine mutants in pin1 by experimental and computational methods
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/7b16f9908d9640838edcda5fed0c2dd7
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Insight into the structural stability of wild-type and histidine mutants in Pin1 by experimental and computational methods

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