Structural differences between wild-type and fish eye disease mutant of lecithin:cholesterol acyltransferase

Yana Reshetnyak, Kissaou T. Tchedre, Maya P. Nair, P. Haydn Pritchard, Andras G. Lacko

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Fluorescence spectroscopy has been used to investigate the conformational changes that occur upon binding of wild type (WT) and mutant (Thr123Ile) lecithin:cholesterol acyltransferase (LCAT) to the potential substrates (dioleoyl-phosphatidyl choline [DOPC] and high density lipoprotein [HDL]). For a detailed analysis of structural differences between WT and mutant LCAT, we performed decompositional analysis of a set of tryptophan fluorescence spectra, measured at increasing concentrations of external quenchers (acrylamide and KI). The data obtained show that Thr123Ile mutation in LCAT leads to a conformation that is likely to be more rigid (less mobile/flexible) than that of the WT protein with a redistribution of charged residues around exposed tryptophan fluorophores. We propose that the redistribution of charged residues in mutant LCAT may be a major factor responsible for the dramatically reduced activity of the enzyme with HDL and reconstituted high density lipoprotein (rHDL).

Original languageEnglish
Pages (from-to)75-82
Number of pages8
JournalJournal of Biomolecular Structure and Dynamics
Volume24
Issue number1
DOIs
StatePublished - Aug 2006

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