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Molecular dynamics simulations integrating kinetics for Pb2+-induced arginine kinase inactivation and aggregation

Paper ID Volume ID Publish Year Pages File Format Full-Text
34329 45018 2015 9 PDF Available
Title
Molecular dynamics simulations integrating kinetics for Pb2+-induced arginine kinase inactivation and aggregation
Abstract

•MD simulations for the action of Pb2+ on the inhibition of alpha-glucosidase.•The predicted docking residues for Pb2+ in the active site of alpha-glucosidase.•The inhibitory effect and binding mechanisms of Pb2+ on alpha-glucosidase.•Structural changes of alpha-glucosidase induced by Pb2+.•Integrating study between inhibition kinetics and computational simulations.

We built a 3D structure of arginine kinase from Exopalaemon carinicauda (ECAK) on the basis of the ORF gene sequence to conduct molecular dynamics simulations between ECAK and Pb2+. As a result, the binding mechanism of Pb2+ to ECAK was predicted from the binding sites, and the structural change was elucidated. To confirm the simulated results, the Pb2+-mediated inhibition and aggregation of ECAK were subsequently conducted. We found that Pb2+ partially inactivated the activity of ECAK with relatively strong binding. The spectrofluorimetry results showed that Pb2+ induced tertiary structural changes of ECAK, with the substantial exposure of hydrophobic surfaces directly induced by ECAK aggregation. The ECAK aggregation process induced by Pb2+ occurred with multi-phase kinetics. The addition of osmolytes did not protect ECAK from Pb2+ inactivation. Because AK plays an important role in the cellular energy metabolism of invertebrates, our study suggests new information about the effect of Pb2+ on ECAK's enzymatic function and unfolding, including aggregation, which may be toxic to invertebrates or may act as a negative regulator.

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Keywords
ECAK, arginine kinase from Exopalaemon carinicauda; ANS, 1-anilinonaphthalene-8-sulfonate; ATP, adenosine triphosphate; MD, molecular dynamicsArginine kinase; Pb2+; MD simulation; Inhibition; Aggregation
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Molecular dynamics simulations integrating kinetics for Pb2+-induced arginine kinase inactivation and aggregation
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Publisher
Database: Elsevier - ScienceDirect
Journal: Process Biochemistry - Volume 50, Issue 5, May 2015, Pages 729–737
Authors
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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