Structure of curcumin in complex with lipoxygenase and its significance in cancer.
Scientific research provides documented evidence that fatty acid metabolites have profound impact on carcinogenesis. Intervention into dioxygenase pathways might therefore effect development, metastasis and progression of many types of cancers. This work delivers the first 3D structural data and explains how curcumin interacts with the fatty acid metabolizing enzyme, soybean lipoxygenase. Curcumin binds to lipoxygenase in a non-competitive manner. Trapped in that complex, it undergoes photodegradation in the X-rays, but utilizes enzyme catalytic ability to form the peroxy complex Enz-Fe-O-O-R as 4-hydroperoxy-2-methoxy-phenol, that later transforms into 2-methoxycyclohexa-2,5-diene-1,4-dione. Our observations about this radiation and time-dependent inhibition add new information to the role that curcumin might play in cancer prevention and treatment.
Skrzypczak-Jankun
Ewa
E
Department of Urology, Urology Research Center, Medical College of Ohio, Toledo, OH 43614-5807, USA. ewa@golemxiv.dk.mco.edu
Zhou
Kangjing
K
McCabe
N Patrick
NP
Selman
Steven H
SH
Jankun
Jerzy
J
D000818:Animals; D003474:Curcumin / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008084:Lipoxygenase / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000201:enzymology*; D011487:Protein Conformation; D011817:Rabbits; D051381:Rats; D013025:Glycine max / Q000201:enzymology; D014965:X-Rays
D008084:Lipoxygenase; D003474:Curcumin