Curcumin and kaempferol prevent lysozyme fibril formation by modulating aggregation kinetic parameters.

Autor:	Borana MS; Department of Chemistry, UM-DAE Centre for Excellence in Basic Sciences, University of Mumbai, Vidhyanagari Campus, Mumbai 400098, India., Mishra P; Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India., Pissurlenkar RR; Molecular Simulations Group, Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Santacruz (East), Mumbai 400098, India., Hosur RV; Department of Chemistry, UM-DAE Centre for Excellence in Basic Sciences, University of Mumbai, Vidhyanagari Campus, Mumbai 400098, India; Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India. Electronic address: hosur@tifr.res.in., Ahmad B; Department of Chemistry, UM-DAE Centre for Excellence in Basic Sciences, University of Mumbai, Vidhyanagari Campus, Mumbai 400098, India. Electronic address: basir.ahmad@cbs.ac.in.
Jazyk:	angličtina
Zdroj:	Biochimica et biophysica acta [Biochim Biophys Acta] 2014 Mar; Vol. 1844 (3), pp. 670-80. Date of Electronic Publication: 2014 Jan 24.
DOI:	10.1016/j.bbapap.2014.01.009
Abstrakt:	Interaction of small molecule inhibitors with protein aggregates has been studied extensively, but how these inhibitors modulate aggregation kinetic parameters is little understood. In this work, we investigated the ability of two potential aggregation inhibiting drugs, curcumin and kaempferol, to control the kinetic parameters of aggregation reaction. Using thioflavin T fluorescence and static light scattering, the kinetic parameters such as amplitude, elongation rate constant and lag time of guanidine hydrochloride-induced aggregation reactions of hen egg white lysozyme were studied. We observed a contrasting effect of inhibitors on the kinetic parameters when aggregation reactions were measured by these two probes. The interactions of these inhibitors with hen egg white lysozyme were investigated using fluorescence quench titration method and molecular dynamics simulations coupled with binding free energy calculations. We conclude that both the inhibitors prolong nucleation of amyloid aggregation through binding to region of the protein which is known to form the core of the protein fibril, but once the nucleus is formed the rate of elongation is not affected by the inhibitors. This work would provide insight into the mechanism of aggregation inhibition by these potential drug molecules. (Copyright © 2014 Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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