Data from: Molecular dynamic simulations reveal the structural determinants of fatty acid binding to oxy-myoglobin

The mechanism(s) by which fatty acids are sequestered and transported in
muscle have not been fully elucidated. A potential key player in this
process is the protein myoglobin (Mb). Indeed, there is a catalogue of
empirical evidence supporting direct interaction of globins with fatty
acid metabolites; however, the binding pocket and regulation of the
interaction remains to be established. In this study, we employed a
computational strategy to elucidate the structural determinants of fatty
acids (palmitic & oleic acid) binding to Mb. Sequence analysis and
docking simulations with a horse (Equus caballus) structural Mb reference
reveals a fatty acid-binding site in the hydrophobic cleft near the heme
region in Mb. Both palmitic acid and oleic acid attain a “U” shaped
structure similar to their conformation in pockets of other fatty
acid-binding proteins. Specifically, we found that the carboxyl head group
of palmitic acid coordinates with the amino group of Lys45, whereas the
carboxyl group of oleic acid coordinates with both the amino groups of
Lys45 and Lys63. The alkyl tails of both fatty acids are supported by
surrounding hydrophobic residues Leu29, Leu32, Phe33, Phe43, Phe46, Val67,
Val68 and Ile107. In the saturated palmitic acid, the hydrophobic tail
moves freely and occasionally penetrates deeper inside the hydrophobic
cleft, making additional contacts with Val28, Leu69, Leu72 and Ile111. Our
simulations reveal a dynamic and stable binding pocket in which the oxygen
molecule and heme group in Mb are required for additional hydrophobic
interactions. Taken together, these findings support a mechanism in which
Mb acts as a muscle transporter for fatty acid when it is in the
oxygenated state and releases fatty acid when Mb converts to deoxygenated
state.