Exposure to hypochlorous acid causes bacterial proteins to unfold and stick to one another, leading to cell death. Credit: Video segment courtesy of the American Chemistry Council. View video
Spring cleaning often involves chlorine bleach, which has been used as a disinfectant for hundreds of years. But our bodies have been using bleach’s active component, hypochlorous acid, to help clean house for millennia. As part of our natural response to infection, certain types of immune cells produce hypochlorous acid to help kill invading microbes, including bacteria.
Researchers funded by the National Institutes of Health have made strides in understanding exactly how bleach kills bacteria—and how bacteria’s own defenses can protect against the cellular stress caused by bleach. The insights gained may lead to the development of new drugs to breach these microbial defenses, helping our bodies fight disease.
In this video, Emad Tajkhorshid of the University of Illinois at Urbana-Champaign explains the molecular dance of transporter proteins, molecules that move substances across the cell membrane.
In this video, Emad Tajkhorshid of the University of Illinois at Urbana-Champaign explains the molecular dance of ABC transporters, a family of molecular machines that utilize ATP to move substances across the cell membrane. Tajkhorshid and his team recently used computational methods to map the movements between two known structural models of MsbA, a bacterial version of a transporter in human cells that helps to export anti-cancer drugs. They then described the individual steps of the molecular motions during the transport cycle. Understanding the process at such a detailed level could suggest new targets for treating a range of diseases, including some drug-resistant cancers that often make more transporter proteins to kick out medications meant to kill them.
The interactions of TMEM24 protein (green) and insulin (red) in pancreatic beta cells are shown in yellow. Credit: Balch Lab, the Scripps Research Institute. View larger image
The identities of the proteins that drive insulin production and release from pancreatic beta cells have largely been a mystery. In new work from the lab of William Balch of the Scripps Research Institute, researchers isolated and then identified all the insulin-bound proteins from mouse beta cells. The results provided a roadmap of the protein interactions that lead to insulin production, storage and secretion. The researchers used the roadmap to identify a protein called TMEM24, which was abundant in beta cells and binds readily to insulin. Balch and his team uncovered that TMEM24, whose involvement in insulin secretion was previously unknown, effectively regulates slower insulin release and could have a key role in maintaining control of glucose levels in the blood. The scientists hope that this roadmap of insulin-interacting proteins will lead to the development of new, targeted approaches to treating type 2 diabetes and a similar insulin-related condition called metabolic syndrome.
Emily Scott Field: Biochemistry Works at: University of Kansas in Lawrence Favorite hobby: Scuba diving Likes watching: “Law & Order” Likes reading: True-life survival stories
Credit: Chuck France, University of Kansas
With an air tank strapped to her back, college student Emily Scott dove to the bottom of the Gulf of Mexico to examine life in an oxygen-starved area called the Dead Zone. The bottom waters had once teemed with red snapper, croaker and shrimp, but to Scott, the region appeared virtually devoid of life. Then, from out of the mud, appeared the long, undulating arms of a brittle star.
As Scott learned, that particular species of brittle star survived in the Dead Zone because it has something many other marine creatures don’t: an oxygen-carrying protein called hemoglobin. This same protein makes our blood red. Key to hemoglobin’s special oxygen-related properties is a small molecular disk called a heme (pronounced HEEM).
Once she saw what it meant to brittle stars, Scott was hooked on heme and proteins that contain it.
Scott’s Findings
Now an associate professor, Scott studies a family of heme proteins called cytochromes P450 (CYP450s). These proteins are enzymes that facilitate many important reactions: They break down cholesterol, help process vitamins and play an important role in flushing foreign chemicals out of our systems.
To better understand CYP450s, Scott uses a combination of two techniques–X-ray crystallography and nuclear magnetic resonance spectroscopy—for capturing the enzymes’ structural and reactive properties.
She hopes to apply her work to design drugs that block certain CYP450 reactions linked with cancer. One target reaction, carried out by CYP2A13, converts a substance in tobacco into two cancer-causing molecules. Another target reaction is carried out by CYP17A1, an enzyme that helps the body produce steroid sex hormones but that, later in life, can fuel the uncontrolled growth of prostate or breast cancer cells.
“I’m fascinated by these proteins and figuring out how they work,” Scott says. “It’s like trying to put together a puzzle—a very addictive puzzle.” Her drive to uncover the unknown and her willingness to apply new techniques have inspired the students in her lab to do the same.
Content adapted from“Hooked on Heme,” an article in the September 2013 issue of Findings magazine.
The image shows a comparison of the predicted binding of the substrate to the active site of HpbD (blue) with the binding sites determined experimentally by crystallography (magenta). Credit: Matt Jacobson, University of California, San Francisco; Steve Almo, Albert Einstein College of Medicine.
Sequencing the genomes of almost 7,000 organisms has identified more than 40 million proteins. But how do we figure out what all these proteins do? New results from an initiative led by John Gerlt of the University of Illinois suggest a possible method for identifying the functions of unknown enzymes, proteins that speed chemical reactions within cells. Using high-powered computing, the research team modeled how the structure of a mystery bacterial enzyme, HpbD, might fit like a puzzle piece into thousands of proteins in known metabolic pathways. Since an enzyme acts on other molecules, finding its target or substrate can shed light on its function. The new method narrowed HpbD’s candidate substrate down from more than 87,000 to only four. Follow-up lab work led to the actual substrate, tHypB, and determined the enzyme’s biological role. This combination of computational and experimental methods shows promise for uncovering the functions of many more proteins.
Learn more:
University of Illinois at Urbana-Champaign News Release
Gerlt Lab
Enzyme Function Initiative
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Exposure to hypochlorous acid causes bacterial proteins to unfold and stick to one another, leading to cell death. Credit: Video segment courtesy of the American Chemistry Council. View video
