NMR reveals molecular interactions and dynamics of fatty acid binding to albumin.
Biochim Biophys Acta. 2013 Aug 9;
Authors: Hamilton JA
Abstract
BACKGROUND: The molecular details of fatty acid (FA) interactions with albumin are fundamental to understanding transport in the plasma and cellular utilization of these key nutrients and building blocks of membranes.
SCOPE OF REVIEW: This review focuses on the development and application of NMR methods to study FA binding to albumin [bovine (BSA) and human (HSA)]. The key strategy was to use (13)C enrichment of a specific carbon in the FA as a non-perturbing probe to permit visualization of the small ligand complexed to the very large protein. NMR contributions to illuminating molecular interactions and FA dynamics are summarized from three decades of studies.
MAJOR CONCLUSIONS: Our early studies detected multiple binding sites that we e hypothesized were distinguished because of the unique tertiary structure of the protein in close proximity to the FA labeled carbon in each site. Later crystallographic structures revealed the presence of polar and charged amino acids side chains near the carboxyl carbon of the FA and unique tertiary structures lining all of the FA binding pockets. In collaboration with the crystallography group, several FA sites in the crystalline state were matched with NMR resonances in the solution state. With the newest application of NMR, 2D NMR spectroscopy detected nine binding sites, and three were located in the crystal structure through displacement of drugs with identified sites.
GENERAL SIGNIFICANCE: NMR spectroscopy utilizing the FA as a probe allows characterization of site-specific interactions, molecular motions within binding sites, the order of filling and removal of FA from sites. This article is part of a Special Issue entitled Serum Albumin.
PMID: 23939311 [PubMed - as supplied by publisher]
DEER in Biological Multispin-Systems: A Case Study on the Fatty Acid Binding to Human Serum Albumin
DEER in Biological Multispin-Systems: A Case Study on the Fatty Acid Binding to Human Serum Albumin
Publication year: 2011
Source: Journal of Magnetic Resonance, In Press, Accepted Manuscript, Available online 10 March 2011</br>
Matthias J.N., Junk , Hans W., Spiess , Dariush, Hinderberger</br>
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