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Effects of hydroxysafflor yellow A on ALDH1: Inhibition kinetics and molecular dynamics simulation

Paper ID Volume ID Publish Year Pages File Format Full-Text
34498 45030 2014 9 PDF Available
Title
Effects of hydroxysafflor yellow A on ALDH1: Inhibition kinetics and molecular dynamics simulation
Abstract

•The inhibitory effect of hydroxysafflor yellow A (HSYA) on acetaldehyde dehydrogenase 1 (ALDH1).•Integrating study between inhibition kinetics and computational molecular dynamics (MD) simulations.•HSYA ligand binding mechanisms to ALDH1.•HSYA potent application for ALDH1-associated human diseases.

Hydroxysafflor yellow A (HSYA) is a potent natural antioxidant that displays important neuroprotective activity. Inhibition of acetaldehyde dehydrogenase 1 (ALDH1) has attracted the attention of researchers due to its overexpression in several types of cancers. We studied the effects of HSYA on ALDH1 by evaluating the inhibitory kinetics based on its antioxidant properties and performing computational simulation integrating methods. HSYA reversibly inhibited human recombinant ALDH1 via non-competitive inhibition (Ki = 0.267 ± 0.024 mM). We also investigated the tertiary structural changes via measuring intrinsic and ANS-binding fluorescence. The results indicated that the inactivation induced by HSYA was associated with structural changes. To obtain further information, we simulated the 3D structure of ALDH1 and conducted computational docking simulations as well as molecular dynamics simulations. The results indicated that 4 rings of HSYA interact with several residues near the ALDH1 active site. Our study provides insight into the inhibition of ALDH1 accompanied by structural changes. Based on its ALDH1-inhibiting effect and its potential as a natural antioxidant, HSYA is a potential agent for treating ALDH1-associated cancers.

Keywords
ALDH1, acetaldehyde dehydrogenase 1; HSYA, hydroxysafflor yellow A; ANS, 1-anilinonaphthalene-8-sulfonate; MD, molecular dynamicsALDH1; Hydroxysafflor yellow A; Inhibition kinetics; Non-competitive inhibitor; Docking simulation; Molecular dynamics
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Effects of hydroxysafflor yellow A on ALDH1: Inhibition kinetics and molecular dynamics simulation
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Publisher
Database: Elsevier - ScienceDirect
Journal: Process Biochemistry - Volume 49, Issue 10, October 2014, Pages 1664–1672
Authors
, , , , , , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us