Allosteric Sensing of Fatty Acid Binding by NMR: Application to Human Serum Albumin.
 

Allosteric Sensing of Fatty Acid Binding by NMR: Application to Human Serum Albumin.

http://www.bionmr.com//www.ncbi.nlm....ed-acspubs.jpg Related Articles Allosteric Sensing of Fatty Acid Binding by NMR: Application to Human Serum Albumin.

J Med Chem. 2016 Aug 25;59(16):7457-65

Authors: Jafari N, Ahmed R, Gloyd M, Bloomfield J, Britz-McKibbin P, Melacini G

Abstract
Human serum albumin (HSA) serves not only as a physiological oncotic pressure regulator and a ligand carrier but also as a biomarker for pathologies ranging from ischemia to diabetes. Moreover, HSA is a biopharmaceutical with a growing repertoire of putative clinical applications from hypovolemia to Alzheimer's disease. A key determinant of the physiological, diagnostic, and therapeutic functions of HSA is the amount of long chain fatty acids (LCFAs) bound to HSA. Here, we propose to utilize (13)C-oleic acid for the NMR-based assessment of albumin-bound LCFA concentration (CONFA). (13)C-Oleic acid primes HSA for a LCFA-dependent allosteric transition that modulates the frequency separation between the two main (13)C NMR peaks of HSA-bound oleic acid (??AB). On the basis of ??AB, the overall [(12)C-LCFA]Tot/[HSA]Tot ratio is reproducibly estimated in a manner that is only minimally sensitive to glycation, albumin concentration, or redox potential, unlike other methods to quantify HSA-bound LCFAs such as the albumin-cobalt binding assay.


PMID: 27429126 [PubMed - indexed for MEDLINE]



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