A hydrophobic loop in Acyl CoA Binding Protein is functionally important for binding to Palmitoyl Coenzyme A. A Molecular Dynamics Study.

VALLEJO D.F.G; GRIGERA J.R.; COSTABEL M.

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

Año: 2008 vol. 42 p. 271 - 277

0141-8130

Acyl-CoA binding protein (ACBP) plays a key role in lipid metabolism, interacting via a partly unknown mechanism with high affinity withlong chain fatty acyl-CoAs (LCFA-CoAs). At present there is no study of the microscopic way ligand binding is accomplished. We analyzed thisprocess by molecular dynamics (MDs) simulations.We proposed a computational model of ligand, able to reproduce some evidence from nuclearmagnetic resonance (NMR) data, quantitative time resolved fluorometry and X-ray crystallography. We found that a hydrophobic loop, not in theactive site, is important for function. Besides, multiple sequence alignment shows hydrophobicity (and not the residues itselves) conservation.© 2007 Elsevier B.V. All rights reserved.Keywords: Acyl-coenzyme A binding protein; Long chain fatty acyl-coenzyme A; Molecular dynamics; Lipid protein interactions; Hydrophobic interaction