“It was really quite a surprise when we realized we had discovered the unknown player in how bacteria make the B vitamin folate, a player that we’ve known of since 1974,” says study author L. Mario Amzel, Ph.D., professor and director of biophysics and biophysical chemistry at Hopkins. “Basic research can be so serendipitous at times.”
Amzel and colleague Maurice Bessman and their labs were in the middle of systematically characterizing how members of a family of related enzymes in bacteria can recognize specific molecules. With each family member, they isolated purified enzyme, grew crystals of pure enzyme, and figured out the enzyme’s 3-D structure by using techniques that use X-rays.
Armed with the 3-D structure, they then used computer modeling to analyze how the enzyme binds to and acts on another molecule, its substrate.
“We still didn’t know that it was anything special until Maurice started searching old publications,” says study author Sandra Gabelli, Ph.D. “As it turns out, Suzuki and coworkers in 1974 had published evidence of an enzyme in the bacteria E. coli with similar characteristics to ours that could initiate folate biosynthesis.”
“So we had to ask, Can the bacteria make folate if we remove the orf17 gene"” says Amzel. Bessman and colleagues then “knocked-out” the gene and, predictably, the bacteria made 10 times less folate than usual.
“It was such a sweet discovery,” says Gabelli. “It’s scientific discovery the old-fashioned way, finding something we weren’t looking for.”
The mechanics behind how bacteria make folate are of particular interest to scientists who want to design more powerful antibacterial drugs. Humans cannot make folate because they do not have any of the same molecular machinery. Therefore, it’s possible to design drugs that target the bacterial folate machinery that would not lead to side effects in humans.
Their discovery, says Amzel, identifies yet another potential antibacterial target. “We are not in that business of drug design—we’re focused on the basics, figuring out how things work,” he says. “We do hope that others can use what we find to make new drugs.”
Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory
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24.03.2017 | Forschungsverbund Berlin e.V.
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
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24.03.2017 | Physics and Astronomy