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Sci Rep. 2019 Jun 10;9(1):8413. doi: 10.1038/s41598-019-44926-5.

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

Author information

1
Key Laboratory of Bio-resources and Eco-environment of the Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610064, P.R. China.
2
Key Laboratory of Bio-resources and Eco-environment of the Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610064, P.R. China. dulinfang@scu.edu.cn.

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.

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