Navigation Links
Scientists take 'snapshots' of enzyme action

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 t ransferring an oxygen atom from the enzyme to the substrate. "Our finding shows that the substrate and cofactor are binding to the enzyme alternately, not together," Swaminathan says.

First, the cofactor (known as NADPH) binds to a molecule known as FAD, which is a coenzyme attached to the FMO, and transfers a hydride ion to it. That makes the FAD group capable of accepting molecular oxygen. Then, when the substrate arrives, the cofactor leaves so that the substrate can bind to the same site on the FAD group. At this moment an oxygen atom from molecular oxygen is attached to the substrate, and the hydride ion obtained from the cofactor combines with the other oxygen atom to form a water molecule, which is released. Once the substrate is oxygenated, it leaves the enzyme and the cofactor binds again.

"With this back-and-forth, alternating binding, the process repeats over and over for continuous turnover of the product," Swaminathan says.

The details of this process may help scientists understand what happens in cases where compounds are not properly metabolized, and possibly develop corrective measures.

One example is a condition called trimethylaminuria, also known as "fish odor syndrome," which results from defective FMOs. Affected individuals are unable to oxygenate trimethylamine, a byproduct of protein digestion released by bacteria living in the gut. People with the disorder release trimethylamine through breath, sweat, and urine, producing a fish-like odor that can be embarrassing and result in psychological effects such as withdrawal and depression.

People with defective FMOs might also suffer additional side effects from drugs, industrial compounds, or other chemicals.


'"/>

Source:DOE/Brookhaven National Laboratory


Related biology news :

1. Scientists ID molecular switch in liver that triggers harmful effects of saturated and trans fats
2. Scientists Replicate Hepatitis C Virus in Laboratory
3. Scientists detect probable genetic cause of some Parkinsons disease cases
4. Scientists find missing enzyme for tuberculosis iron scavenging pathway
5. Scientists seek answers on what activates deadly anthrax spores
6. Yale Scientists Find MicroRNA Regulates Ras Cancer Gene
7. Scientists collaborate to assess health of global environment
8. Scientists decipher genome of fungus that can cause life-threatening infections
9. Scientists discover the cellular roots of graying hair
10. Scientists rid stem cell culture of key animal cells
11. Scientists develop new color-coded test for protein folding
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/11/2017)... , April 11, 2017 NXT-ID, ... security technology company, announces the appointment of independent Directors Mr. ... to its Board of Directors, furthering the company,s corporate ... ... NXT-ID, we look forward to their guidance and benefiting from ...
(Date:4/4/2017)...   EyeLock LLC , a leader of iris-based ... Patent and Trademark Office (USPTO) has issued U.S. Patent ... an iris image with a face image acquired in ... 45 th issued patent. "The ... the multi-modal biometric capabilities that have recently come to ...
(Date:3/29/2017)... 29, 2017  higi, the health IT company that ... North America , today announced a Series B ... of EveryMove. The new investment and acquisition accelerates higi,s ... to transform population health activities through the collection and ... higi collects and secures data today on behalf ...
Breaking Biology News(10 mins):
(Date:10/10/2017)... DIEGO, CALIF. (PRWEB) , ... October 10, 2017 , ... ... as part of its corporate rebranding initiative announced today. The bold new look ... its reach, as the company moves into a significant growth period. , It will ...
(Date:10/10/2017)... DALLAS , Oct. 10, 2017 International research firm ... IoT Strategy, will speak at the TMA 2017 Annual Meeting , ... key trends in the residential home security market and how smart safety ... ... "The ...
(Date:10/9/2017)... Oct. 9, 2017  BioTech Holdings announced today ... which its ProCell stem cell therapy prevents limb ... The Company, demonstrated that treatment with ProCell resulted ... saved as compared to standard bone marrow stem ... resulted in reduction of therapeutic effect.  ...
(Date:10/9/2017)... , ... October 09, 2017 ... ... on October 5, 2017, in the medical journal, Epilepsia, Brain Sentinel’s SPEAC® ... gold standard, video EEG, in detecting generalized tonic-clonic seizures (GTCS) using surface ...
Breaking Biology Technology: