Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Impact of Bilirubin on 7α- and 7β- Hydroxysteroid Dehydrogenases: Spectra and Docking Analysis

Version 1 : Received: 18 April 2023 / Approved: 19 April 2023 / Online: 19 April 2023 (07:35:44 CEST)

A peer-reviewed article of this Preprint also exists.

Ji, Q.; Chen, J.; Zhu, L.; Wang, R.; Wang, B. The Impact of Bilirubin on 7α- and 7β-Hydroxysteroid Dehydrogenases: Spectra and Docking Analysis. Catalysts 2023, 13, 965. Ji, Q.; Chen, J.; Zhu, L.; Wang, R.; Wang, B. The Impact of Bilirubin on 7α- and 7β-Hydroxysteroid Dehydrogenases: Spectra and Docking Analysis. Catalysts 2023, 13, 965.

Abstract

7α- and 7β-hydroxysteroid dehydrogenases (HSDH) are a pair of enzymes that can catalyze the isomerization of hydroxyl group at site 7 of bile acids. In previous study, we found that the activities of 7α- and 7β-HSDH can be inhibited by bilirubin. In order to clarify the impact, the effects of bilirubin on enzymes were studied by kinetics, spectrum and docking analysis. Relative activity of 7α-HSDH remained less than 40 % under 1 mM bilirubin, for 7β-HSDH, only 18 % activity left at the same condition. Using taurochenodeoxycholic acid (TCDCA) as substrate, the Km of 7α-HSDH was up to 0.63 mM from 0.24 mM after binding with bilirubin, the Km of 7β-HSDH rose from 1.14 mM to 1.87 mM for the catalysis of tauroursodeoxycholic acid (TUDCA). The affinity of 7α- and 7β-HSDH to substrate decreased with the effect of bilirubin. The binding of bilirubin with 7α- or 7β-HSDH were analyzed by UV–Vis spectra, Fluorescence spectra and Circular dichroism (CD) spectra. The results reflected that bilirubin caused a slight change in the secondary structure of 7α- or 7β-HSDH, and the changes were correlated with the ratio of bilirubin to enzyme. 10 candidate molecular docking results were presented to reflect the binding of bilirubin with 7α- or 7β-HSDH and to explore the inhibition mechanism. This research not only provides the more in-depth understanding of 7α- and 7β-HSDH, but also reminds us to avoid the inhibition of bilirubin on hydroxysteroid dehydrogenases.

Keywords

Bilirubin; 7α- and 7β-hydroxysteroid dehydrogenases; Activity; Inhibition

Subject

Biology and Life Sciences, Biology and Biotechnology

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