RT Journal Article
T1 On the Regio‐ and Stereospecificity of Arachidonic Acid Peroxidation Catalyzed by Mammalian 15‐Lypoxygenases: A Combined Molecular Dynamics and QM/MM Study
A1 Suardíaz Delrío, Reynier
A1 Masgrau, Laura
A1 Lluch, José
A1 González‐Lafont, Àngels
AB 15-Lipoxygenases (15-LOs) catalyse the peroxidation reaction of arachidonic acid (AA) in mammals with remarkable regioand stereospecificity. This positional-specific peroxidation is of paramount importance because it determines the nature and biological functions of the final metabolites generated by each LO as a result of the oxidative metabolism of AA. Although several hypotheses have been formulated concerning the regio- and stereospecificity of LOs, the molecular basis of such behaviour is still unclear. Herein, we combined quantum mechanics/molecular mechanics calculations with molecular dynamics simulations of the complete rabbit 15-LO/AA solvated model to examine the most accepted hypotheses for the regio- and stereospecificity of LOs. We have found that the clue to explain this specificity is the oxygen-targeting hypothesis through steric shielding of specific residues (mainly Leu597, Gln548 and Phe175, as well as the AA tail itself). Our deductions are based primarily on the analysis of the energy barrier heights from the oxygen addition reaction profiles
PB Wiley
SN 1439-4235
YR 2013
FD 2013
LK https://hdl.handle.net/20.500.14352/92499
UL https://hdl.handle.net/20.500.14352/92499
LA eng
NO Suardíaz, Reynier, et al. «On the Regio‐ and Stereospecificity of Arachidonic Acid Peroxidation Catalyzed by Mammalian 15‐Lypoxygenases: A Combined Molecular Dynamics and QM/MM Study». ChemPhysChem, vol. 14, n.o 16, noviembre de 2013, pp. 3777-87. https://doi.org/10.1002/cphc.201300629.
NO Ministerio de Economía y Competitividad (España)
NO Generalitat de Catalunya
NO Alianza 4U
DS Docta Complutense
RD 7 abr 2025