Document Detail

Insight into the interaction sites between fatty acid binding proteins and their ligands.
MedLine Citation:
PMID:  19834748     Owner:  NLM     Status:  MEDLINE    
Fatty acid binding proteins (FABPs), are evolutionarily conserved small cytoplasmic proteins that occur in many tissue-specific types. One of their primary functions is to facilitate the clearance of the cytoplasmic matrix from free fatty acids and of other detergent-like compounds. Crystallographic studies of FABP proteins have revealed a well defined binding site located deep inside their beta-clam structure that is hardly exposed to the bulk solution. However, NMR measurements revealed that, when the protein is equilibrated with its ligands, residues that are clearly located on the outer surface of the protein do interact with the ligand. To clarify this apparent contradiction we applied molecular dynamics simulations to follow the initial steps associated with the FABP-fatty acid interaction using, as a model, the interaction of toad liver basic FABP, or chicken liver bile acid binding protein, with a physiological concentration of palmitate ions. The simulations (approximately 200 ns of accumulated time) show that fatty acid molecules interact, unevenly, with various loci on the protein surface, with the favored regions being the portal and the anti-portal domains. Random encounters with palmitate at these regions led to lasting adsorption to the surface, while encounters at the outer surface of the beta-clam were transient. Therefore, we suggest that the protein surface is capable of sequestering free fatty acids from solution, where brief encounters evolve into adsorbed states, which later mature by migration of the ligand into a more specific binding site.
Lihie Ben-Avraham Levin; Assaf Ganoth; Shay Amram; Esther Nachliel; Menachem Gutman; Yossi Tsfadia
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Publication Detail:
Type:  Journal Article     Date:  2009-10-16
Journal Detail:
Title:  Journal of molecular modeling     Volume:  16     ISSN:  0948-5023     ISO Abbreviation:  J Mol Model     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-03-26     Completed Date:  2010-06-23     Revised Date:  2013-03-15    
Medline Journal Info:
Nlm Unique ID:  9806569     Medline TA:  J Mol Model     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  929-38     Citation Subset:  IM    
Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
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MeSH Terms
Binding Sites / genetics
Carrier Proteins / analysis,  genetics,  metabolism*
Fatty Acid-Binding Proteins / analysis,  genetics,  metabolism*
Fatty Acids / chemistry,  genetics,  metabolism*
Liver / chemistry,  metabolism
Membrane Glycoproteins / analysis,  genetics,  metabolism*
Molecular Dynamics Simulation
Reg. No./Substance:
0/Carrier Proteins; 0/Fatty Acid-Binding Proteins; 0/Fatty Acids; 0/Ligands; 0/Membrane Glycoproteins; 0/bile acid binding proteins

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