Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Structure of a Protein Related to Heart and Nervous System Health Revealed

17.11.2010
May lead to smarter drug design, better understanding of a genetic disorder of the cardiovascular system

University of Michigan researchers have solved the structure of a protein that is integral to processes responsible for maintaining a healthy heart and nervous system.

The protein structure in question is cystathionine beta-synthase, known as CBS. CBS uses vitamin B6 to make hydrogen sulfide (H2S), a gaseous signaling molecule that helps maintain a healthy heart and nervous system. H2S also induces a state of suspended animation or hibernation in animals by decreasing body temperature and lowering metabolic rate.

The work to decode the structure was led by Ruma Banerjee, Ph.D., a professor in the Department of Biological Chemistry at the U-M Medical Schoool, Janet Smith, Ph.D., a research professor at the U-M Life Sciences Institute, and their colleagues. Their findings are published today in the Proceedings of the National Academy of Sciences.

"The structure of full-length CBS, which has eluded the science community for more than a decade, provides a wealth of new information about gas generation by CBS, which is especially important in the brain,” says Banerjee, the study’s senior author and the Vincent Massey Collegiate Professor of Biological Chemistry and associate chair of biological chemistry . “It also provides a framework for understanding homocystinuria-causing mutations."

Mutations in the gene for CBS cause homocystinuria, an inherited disorder that affects the central nervous system, ocular, skeletal, and cardiovascular systems.

The structure of the full-length CBS, seen here for the first time, provides a molecular explanation for homocystinuria due to CBS defects.

The activity of CBS is increased by SAMe (S-adenosylmethionine), a dietary supplement that is used for its anti-depressant and anti-inflammatory activities. SAMe also increases production of H2S by binding to CBS.

“Molecular insights into the architecture of the CBS domain to which SAMe binds open doors to rational drug design for fine-tuning H2S production for pharmaceutical purposes,” says colleague Markos Koutmos, Ph.D., a research investigator in Smith’s research group .

“We captured the CBS enzyme at two points in its complex chemical reaction by trapping two highly reactive chemical intermediates in the active site of the enzyme,” says researcher Omer Kabil, Ph.D., a postdoctoral fellow in Banerjee’s lab. The structures of these trapped species reveal details of how vitamin B6 helps CBS perform the complex chemical reactions leading to H2S production.

“The important chemical details we see in CBS can be applied to understanding the other human enzymes that depend on vitamin B6, of which there are more than 50,” says Smith, who in addition to her LSI position is also the Martha L. Ludwig Professor of Protein Structure & Function in the Department of Biological Chemistry of the Medical School.

This work was supported by grants from the National Institutes of Health.

Jennifer Farina | Newswise Science News
Further information:
http://www.umich.edu

More articles from Life Sciences:

nachricht New catalyst controls activation of a carbon-hydrogen bond
21.11.2017 | Emory Health Sciences

nachricht The main switch
21.11.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

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,...

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

Previous evidence of water on mars now identified as grainflows

21.11.2017 | Physics and Astronomy

NASA's James Webb Space Telescope completes final cryogenic testing

21.11.2017 | Physics and Astronomy

New catalyst controls activation of a carbon-hydrogen bond

21.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>