Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

One-Way Street or Two-Way Traffic – How Enzymes adjust to the environmental conditions in the cell

08.06.2005


More effective and safer medicines will be possible if we understand how the body detoxifies itself. The cytochrome P450 enzymes are the molecular machines responsible for the disposal by the human body of 80% of all medicines. These enzymes are also needed for the body to remove poisons and to manufacture many important molecules such as the sex hormones progesterone and testosterone. Understanding how the cytochromes P450 function is of great importance for human health.



New insight into how this family of enzymes functions has been provided by scientists at EML Research, in Heidelberg, Germany. Using computers to simulate how a mammalian cytochrome P450 interacts with chemicals such as progesterone, they now have an understanding of the ways into and out of the center of this protein. The functional part of the cytochromes P450 is buried in their centre, so understanding chemical access is critical to understanding the enzyme’s function. The new simulations show a channel that is different to those seen in the cytochromes P450 found in bacteria. However, the researchers propose that the mammalian enzyme may use the newly discovered channel and the channel seen in the bacterial enzymes, depending upon its cellular environment and the chemical compound that is entering it.

The scientists at EML Research propose two mechanisms in the newly investigated cytochrome P450: (1), a ‘one-way’ route whereby fat-soluble (lipophilic) substrates enter the enzyme from the membrane, and products leave the active site, via the newly discovered channel, directly into solvent; and (2) a ‘two-way’ route for access and egress of water-soluble compounds solely via the new channel. The proposed differences in the substrate access and product egress routes between the mammalian and bacterial cytochromes P450 highlights the adaptability of the P450 family to the requirements of different cellular locations and substrate specificity profiles.


The article (with videoclips from the simulations in the online-version) is published in: EMBO Reports, (2005) 6, 6, 584–589. doi:10.1038/sj.embor.7400420. Karin Schleinkofer, Sudarko, Peter J. Winn, Susanne K. Lüdemann, Rebecca C. Wade: Do mammalian cytochrome P450 show multiple ligand access pathways and ligand channeling?

The EML Research gGmbH (http://www.eml.research.de) is a non-profit institute conducting research in Information Technology and its applications. A strong focus is set on bioinformatics. Research is carried out in close collaboration with universities and other research institutes. EML Research projects are supported by the Klaus Tschira Foundation (KTS) (http://www.kts.villa-bosch.de), as well as by the European Union, the German Ministry of Research and Education (BMBF) and by the German Research Foundation (DFG). EML Research is a partner in the first German Center for Modeling and Simulation in the Biosciences (BIOMS, www.bioms.de). KTS and EML Research are housed in the Villa Bosch in Heidelberg, the former residence of Nobel Prize laureate Carl Bosch (1874 – 1940).

Rebecca Wade | alfa
Further information:
http://www.eml-research.de

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>