Fatty Acid Binding Proteins: Same Structure but Different Binding Mechanisms? Molecular Dynamics Simulations of Intestinal Fatty Acid Binding Protein.
From: Laser Laboratory for Fast Reactions in Biology, Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, Israel.
Biophysical journal
- Publish Date: Mar 2006
- ISSN: 0006-3495
- Volume: 90
- Issue: 5
- Pages: 1535-45
- Medium: Print
- Language: English
- Citation (JAMA): Friedman Ran, Nachliel Esther, Gutman Menachem, et al. Fatty Acid Binding Proteins: Same Structure but Different Binding Mechanisms? Molecular Dynamics Simulations of Intestinal Fatty Acid Binding Protein.. Biophys. J. Mar 2006;90:1535-45
Abstract
Fatty acid binding proteins (FABPs) carry fatty acids (FAs) and other lipids in the cellular environment, and are thus involved in processes such as FA uptake, transport, and oxidation. These proteins bind either one or two ligands in a binding site, which appears to be inaccessible from the bulk. Thus, the entry of the substrate necessitates a conformational change, whose nature is still unknown. A possible description of the ligand binding process is given by the portal hypothesis, which suggests that the FA enters the protein through a dynamic area known as the portal region. On the other hand, recent simulations of the adipocyte lipid binding protein (ALBP) suggested a different entry site (the alternative portal). In this article, we discuss molecular dynamics simulations of the apo-intestinal-FABP (I-FABP) in the presence of palmitate molecule(s) in the simulation box. The simulations were carried out to study whether the FA can enter the protein during the simulations (as in the ALBP) and where the ligand entry site is (the portal region, the alternative portal or a different domain). The analysis of the simulations revealed a clear difference between the ALBP and the I-FABP. In the latter case, the palmitate preferentially adsorbed to the portal region, which was more mobile than the rest of the protein. However, no ligand entry was observed in the multi-nanosecond-long simulations, in contrast to ALBP. These findings suggest that, although the main structural motif of the FABPs is common, the fine details of each individual protein structure grossly modulate its reactivity.
Mesh Headings (Keywords): Adsorption, Binding Sites, Computer Simulation, Fatty Acid-Binding Proteins, Kinetics, Models, Chemical, Models, Molecular, Palmitic Acid, Protein Binding, Protein Conformation
Check for Full Text / PubMed Unique Identifier (PMID): 16361342
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