The role of Lys525 on the head-group anchoring of fatty acids in the highest affinity binding site of albumin
Issue title: From Molecule to Tissue: XIII European Conference on the Spectroscopy of Biological Molecules, Palermo, Italy, August 28–September 2, 2009, Part 1 of 2
Affiliations: LiCryL CNR-INFM and CEMIF.Cal, University of Calabria, 87036 Rende, Italy | Department of Physics and Unità CNISM, University of Calabria, 87036 Rende, Italy
Note: [] Corresponding author: Bruno Rizzuti, LiCryL CNR-INFM and CEMIF.Cal, University of Calabria, 87036 Rende, Italy. Tel.: +39 0984 49 6078; Fax: +39 0984 49 4401; E-mail: bruno.rizzuti@cnr.it.
Abstract: Human serum albumin provides the transport of long-chain fatty acids in the blood through three high-affinity and four low-affinity binding sites. Molecular dynamics simulations have been performed to investigate the anchoring of palmitic acid molecules to the protein. In the site with the highest affinity, Site 5, the key residue Lys525 not only binds the head-group of the palmitate ion by electrostatic interactions with its charged terminal group, but it also accommodates the first portion of the lipid chain by non-electrostatic interactions with the rest of its sidechain. The flexibility of Lys525, and in particular of the dihedral angle χ3, is suggested to account for a number of spectroscopic properties observed in correspondence with the entrance of the hydrophobic pocket constituting Site 5.
