Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

First structure of transporter enzyme family is solved

01.08.2003


Finding will aid drug design to combat depression, stroke and diabetes. Scientists are a step closer to understanding how essential nutrients, vitamins and minerals are ferried into cells.



For the first time, a member of the Major Facilitator Superfamily (MFS) of transport proteins, found in almost every form of life, has been visualised by researchers from Imperial College London and the University of California, Los Angeles.

Reporting in Science today, the researchers reveal the structure of lactose permease, the enzyme in Esherichia coli that helps pump lactose, the major sugar in milk, into cells. Using the structure data, the researchers propose a possible mechanism of action, which is likely to be common among other transport proteins in this family.


Professor So Iwata of Imperial’s Centre for Structural Biology and senior author of the paper explains: "Membrane transport proteins play major roles in depression, stroke and diabetes. Unravelling their structure is critical not only for understanding how we function, but also to improve drug design. Indeed, two of the most widely prescribed drugs in the world, Prozac and Prilosec, act through these proteins.

"The three-dimensional structure of lactose permease gives us our first real picture of how the family of enzymes work. For example, in humans the MFS transporter GLUT4 is responsible for increased glucose uptake in response to insulin stimulation, which has important implications for diabetes. Using the structure of lactose permease we can model GLUT4 and design drugs to control glucose uptake."

Membrane transport proteins play a crucial role in maintaining the selective internal environment of cells. They act as gatekeepers by controlling the entry of nutrients and the exit of waste products. But only four transport protein structures are presently known, compared with over 30,000 soluble protein structures, because they are notoriously difficult to crystallise.

Professor Iwata’s Laboratory of Membrane Protein Crystallography is one of a small number around the world that focuses on determining the three-dimensional structure of membrane embedded proteins.

By combining expertise with Professor Ron Kaback of the University of California, who has been working on lactose permease for 30 years, they have finally solved the structure of this important protein.

Previous biochemical studies had identified six sites within the genetic code of lactose permease that are thought to be crucial to transportation. Using the latest X-ray crystallography techniques, the researchers were able to visualise how lactose permease binds to sugar.

"We have been able to pinpoint areas in the genetic code critical for binding and transport of sugar, which are consistent with information derived from biochemical studies, "said Professor Iwata.

By combining the structural data with previous findings the researchers propose a mechanism of enzyme action.

"Computer simulations show that the enzyme works in a surprisingly simple way. The enzyme is literally gate-keeping. Usually the gate is open towards the outside of the cells and various substances can reach the sugar-binding pocket in the middle of the enzyme, embedded in the cell membrane.

"Only when the enzyme identifies lactose does the other gate, connected to the inside of the cell, open and let the sugar go through. This process is driven by energy called the ’proton motive force’ and should be common among membrane transport proteins."

Professor Iwata added: "Only 40 years ago the idea that genes could be specifically turned on or off in response to different environmental conditions was revolutionary. It was studies in E. coli that showed the bacterial cellular machinery needed to digest lactose is only activated when glucose is not available. Now we have a detailed molecular understanding of how lactose permease contributes to this process."

Judith H Moore | EurekAlert!
Further information:
http://www.imperial.ac.uk

More articles from Life Sciences:

nachricht Carefully crafted light pulses control neuron activity
20.11.2017 | University of Illinois at Urbana-Champaign

nachricht Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Heavy nitrogen molecules reveal planetary-scale tug-of-war

20.11.2017 | Earth Sciences

Taking a spin on plasma space tornadoes with NASA observations

20.11.2017 | Physics and Astronomy

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>