Scientists at the U.S. Department of Energy's Brookhaven National Laboratory, the New York Structural Biology Center, and SGX Pharmaceuticals, Inc., have determined the atomic crystal structure and functional mechanism of an enzyme essential for eliminating unwanted, non-nutritional compounds such as drugs, industrial chemicals, and toxic compounds from the body. The detailed mechanism of action will help scientists understand how these compounds are eliminated and what goes wrong in cases where normal metabolism fails. The research will be published online the week of June 12, 2006, by the Proceedings of the National Academy of Sciences.
According to Brookhaven biologists Eswaramoorthy Subramaniam, the lead author, and Subramanyam Swaminathan, who led the research, most non-nutritional, foreign substances such as drugs and industrial chemicals are insoluble in water. The body uses two main groups of enzymes -- flavin-containing monooxygenases (FMOs) and cytochrome P450s -- to convert these compounds to soluble forms that can be easily excreted.
"For FMOs, the end result -- that an oxygen atom gets added to make these compounds soluble -- is simple," Swaminathan says, "but the reactions require additional participants, or cofactors." In order to understand the molecular mechanism, the scientists used high-intensity x-ray beams at the National Synchrotron Light Source (NSLS) to identify the positions of individual atoms and produce crystal structures of the enzyme, the enzyme plus its cofactor, and the enzyme plus the cofactor plus the compound to be oxidized (the substrate).
"These crystal structures give step-by-step snapshots of different stages of the catalytic action," Swaminathan says, "and reveal a mechanism that is different from what had been known about this process."
Previously, it had been believed that all the "players" -- the enzyme, cofactor, and substrate -- came together at a particular time to perform the function of tPage: 1 2 Related biology news :1
Source:DOE/Brookhaven National Laboratory
. Scientists ID molecular switch in liver that triggers harmful effects of saturated and trans fats2
. Scientists Replicate Hepatitis C Virus in Laboratory3
. Scientists detect probable genetic cause of some Parkinsons disease cases4
. Scientists find missing enzyme for tuberculosis iron scavenging pathway5
. Scientists seek answers on what activates deadly anthrax spores6
. Yale Scientists Find MicroRNA Regulates Ras Cancer Gene7
. Scientists collaborate to assess health of global environment8
. Scientists decipher genome of fungus that can cause life-threatening infections9
. Scientists discover the cellular roots of graying hair10
. Scientists rid stem cell culture of key animal cells11
. Scientists develop new color-coded test for protein folding