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
2006 Journal of Biomolecular Structure and Dynamics  
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
more » ... ncentrations 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).
doi:10.1080/07391102.2006.10507101 pmid:16780378 fatcat:u74rzimisngvxn3nb6nea7t5au