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 What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Porous crystalline materials: TU Graz researcher shows method for controlled growth

07.12.2016 | Materials Sciences

Simple processing technique could cut cost of organic PV and wearable electronics

06.12.2016 | Materials Sciences

3-D printed kidney phantoms aid nuclear medicine dosing calibration

06.12.2016 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>