Curcumin inhibits lipoxygenase by binding to its central cavity: theoretical and X-ray evidence.
Many lipoxygenase inhibitors including curcumin are currently being studied for their anti-carcinogenic properties. Curcumin is a naturally occurring polyphenolic phytochemical isolated from the powdered rhizome of the plant Curcuma longa that possesses anti-inflammatory properties and inhibits cancer formation in mice. Recently it was shown that the soybean lipoxygenase L1 catalyzed the oxygenation of curcumin and that curcumin can act as a lipoxygenase substrate. In the current study, we investigated the fate of curcumin when used as a soybean lipoxygenase L3 substrate. By use of X-ray diffraction and mass spectrometry, we found an unoccupied electron mass that appears to be an unusual degradation product of curcumin (4-hydroxyperoxy-2-methoxyphenol) located near the soybean L3 catalytic site. Understanding how curcumin inhibits lipoxygenase may help in the development of novel anti-cancer drugs used for treatment where lipoxygenases are involved.
Skrzypczak-Jankun
E
E
Instrumentation Center, College of Art and Sciences, The University of Toledo, Toledo, OH 43606, USA.
McCabe
N P
NP
Selman
S H
SH
Jankun
J
J
D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003474:Curcumin / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism*; D013058:Mass Spectrometry; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011485:Protein Binding; D030262:Soybean Proteins / Q000378:metabolism
D004791:Enzyme Inhibitors; D030262:Soybean Proteins; C095864:lipoxygenase 3; D008084:Lipoxygenase; D003474:Curcumin