Compact oleic acid in HAMLET |
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Authors: | Fast Jonas Mossberg Ann-Kristin Nilsson Hanna Svanborg Catharina Akke Mikael Linse Sara |
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Affiliation: | Department of Biophysical Chemistry, Lund University, P.O. Box 124, SE-221 00 Lund, Sweden. jfast@colorado.edu |
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Abstract: | HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a complex between alpha-lactalbumin and oleic acid that induces apoptosis in tumor cells, but not in healthy cells. Heteronuclear nuclear magnetic resonance (NMR) spectroscopy was used to determine the structure of 13C-oleic acid in HAMLET, and to study the 15N-labeled protein. Nuclear Overhauser enhancement spectroscopy shows that the two ends of the fatty acid are in close proximity and close to the double bond, indicating that the oleic acid is bound to HAMLET in a compact conformation. The data further show that HAMLET is a partly unfolded/molten globule-like complex under physiological conditions. |
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Keywords: | CD, circular dichroism EDTA, ethylenediamintetraacetic acid HAMLET, human alpha-lactalbumin made lethal to tumor cells HSQC, heteronuclear single quantum correlation MD, molecular dynamics NMR, nuclear magnetic resonance NOESY, nuclear Overhauser enhancement spectroscopy |
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