Lipoxygenases (LOX) are found in many organisms and oxidize polyunsaturated fatty acids to hydroperoxides. The first tertiary structures predicted already 30 years ago a dedicated oxygen channel to the non-heme iron metal center, which has been a topic of discussion ever since. Analysis of more than fifteen lipoxygenases revealed (mostly) conserved channels from the iron metal center to the surface. They were lined by residues of α-helices 9 and 11 and characteristically passed through a loop between two β strands below the surface. The channel orifices were generally open and the other ends were opposite the metal center and linked to substrate cavities by residues at mainly conserved positions of α-helices 9 and 11, which included the Gly/Ala switch and nearby residues. Two observations suggest that they mediate oxygen perfusion. Investigations of 15 S -LOX1 and soybean LOX1 by molecular dynamic analysis and replacements in the middle of the channels with bulky residues reduced the perfusion of oxygen and altered substrate turnover and the products. This review revealed a common channel design but with heterogeneity between animal, plant and a subfamily of fungal lipoxygenases with iron replaced by manganese. Their tertiary structures can now be compared and investigated for perfusion of O 2 . • Lipoxygenases (LOXs) oxidize polyunsaturated fatty acids by insertion of O 2. • An O 2 channel to the active site was predicted 30 years ago and debated ever since • Experiments support 0 2 channels in two LOXs but structural information is limited • Structural analysis of over 15 LOXs revealed O 2 channels with common features • They connected the surface to residues of catalytic importance at the active site
Ernst Oliw (Sun,) studied this question.