Exploring allosteric properties of mammalian ALOX15: octyl (<i>N</i>-(4-(benzofuran-2-yl)-2-methoxyphenyl)sulfamoyl)- and octyl (<i>N</i>-(4-(1<i>H</i>-indol-2-yl)-2-methoxyphenyl)sulfamoyl)carbamates as ALOX inhibitors.

ABSTRACT: Mammalian ALOX15 are allosteric enzymes but the mechanism of allosteric regulation remains a matter of discussion. Octyl (N-(5-(1H-indol-2-yl)-2-methoxyphenyl)sulfamoyl)carbamate inhibits the linoleate oxygenase activity of ALOX15 at nanomolar concentrations, but oxygenation of arachidonic acid is hardly affected. The mechanism of substrate selective inhibition suggests inter-monomer communication within the allosteric ALOX15 dimer complex, in which the inhibitor binding to monomer A induces conformational alterations in the structure of the active site of monomer B. Interactions of the NH-group of the indole moiety with the Fe(iii)-OH^- cofactor or of the SO₂ group of the sulfocarbamate moiety with the side chain NH₂ group of Gln596 may be imp

SUBMITTER: Gavrilyuk V 

PROVIDER: S-EPMC12415691 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature