Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Barrel structure in globular proteins may transport small molecules

11.06.2003


The ability of proteins to guide small molecules to reaction sites and across membranes is essential to many metabolic pathways, but the process is not well understood. Now, scientists at the University of Illinois at Urbana-Champaign have shown that a globular protein with a barrel structure can direct small molecules in much the same fashion as a membrane protein.



Chemistry professor Zaida Luthey-Schulten, graduate student Rommie Amaro, and Emad Tajkhorshid, assistant director of physics research at the university’s Beckman Institute for Advanced Science and Technology, used molecular dynamics simulations to study the movement of ammonia during the biosynthesis of the amino acid histidine. A paper describing the results is to be published the week of June 9 in the Online Early Edition of the Proceedings of the National Academy of Sciences. The print version will appear at a later date.

Most living organisms are composed of a set of 20 amino acids, the so-called "building blocks of life." Each of these amino acids is produced through what can be thought of as a biological assembly line. Starting with a small part, subsequent parts are added or removed by enzymes until the final compound is formed. These final compounds become the major components of proteins and tissues.


For humans, the 20 amino acids can be divided into two groups: Eleven are made by the human body and are called "nonessential"; the other nine are not made by the body and are called "essential." Despite their names, all 20 amino acids are crucial to human health. One of the main reasons nutritionists advise people to eat balanced diets is because the nine essential amino acids must be ingested and are found in different foods.

Histidine is one of the nine essential amino acids. Because histidine is a critical component of nearly all living systems, understanding how it is made is of great interest. Histidine’s biological assembly line consists of nine steps. Of special interest is the fifth step, where an event called substrate channeling may occur.

"Imagine that you need to move an object from one point to another, but there is a mountain standing in the way," Amaro said. "You could drive over the mountain, you could drive around it, or you could make a tunnel and drive through it. The tunneling option, referred to as substrate channeling in proteins, is what appears to be happening in this fifth step."

Although substrate channeling is a recurring theme in biological organisms, "this is the first time this particular enzyme -- a so-called alpha-beta barrel -- has been suggested to use its barrel structure as this type of channel," Amaro said.

In bacterial cells, the fifth step of histidine synthesis begins when two proteins (hisH and hisF) come together. Once the proteins dock, a reaction occurs at the "active site" of hisH, releasing a molecule of ammonia. Studies have suggested that this ammonia molecule then diffuses across the interface and enters the hisF protein.

"This protein looks like an empty barrel; it has a narrow channel running down the center," Luthey-Schulten said. "The ammonia enters the channel, travels through it, and is then used in another reaction that takes place at the opposite end."

Using molecular dynamics simulations developed in the Theoretical and Computational Biophysics group at the Beckman Institute, and in conjunction with the National Center for Supercomputing Applications, the researchers were able to simulate this protein function.

"We applied a force to ammonia to pull it through the channel of the hisF protein and then watched what happened," Luthey-Schulten said. "Our studies show that it is indeed possible -- even energetically favorable -- for ammonia to use the barrel as a channel to undergo protected and directed travel from one active site to another."

Another interesting aspect of the system is that there appears to be a "gate" at the mouth of the barrel. "In all of the available crystal structures, the gate appears to be closed," Amaro said. "When the gate is closed, it is nearly impossible for the ammonia molecule to pass through. Therefore, the reaction -- and more importantly, the synthesis of histidine -- can happen only when the gate opens."

The exact mechanism of the gate opening is not known, Luthey-Schulten said. "We modeled one possible open-gate configuration and found that the energy required for the ammonia to pass into the barrel was much more reasonable."

The simulations suggest that globular proteins, like membrane proteins, can exploit their structure to transport small molecules.

"This is an excellent example of channeling between two catalytic enzymatic sites," Tajkhorshid said. "Generating the ammonia molecule and then delivering it directly to the reaction site means it won’t get lost in solution. This is a very efficient way of increasing the rate of a chemical reaction."


###
The National Science Foundation funded the work.

James E. Kloeppel | UIUC
Further information:
http://www.uiuc.edu/
http://www.news.uiuc.edu/scitips/03/0610ammonia.html
http://www.beckman.uiuc.edu/

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>