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
Gene therapy shows promise for treating Niemann-Pick disease type C1
27.10.2016 | NIH/National Human Genome Research Institute
'Neighbor maps' reveal the genome's 3-D shape
27.10.2016 | International School of Advanced Studies (SISSA)
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
27.10.2016 | Materials Sciences
27.10.2016 | Physics and Astronomy
27.10.2016 | Life Sciences