science news

Insights into HIV-1 RNA dimerization: two RNA genomes are packaged in every infectious HIV particle, and they are joined by a specific mechanism at specific sites along the molecules. Researchers at NIST and CARB have shown that specific protonation of the dimerization initiation sequence loop residue A272 may be involved in dimer maturation. Read the abstract and, if you have access, get the PNAS preprint from here. If confirmed in vivo, this will be a novel role for protonation in RNA structure modulation.


vitE.jpgNew antioxidants: by chopping off its tail and substituting nitrogen into the two rings, Derek Pratt and colleages at Vanderbilt University have turned alpha-tocopherol (the most active in humans of 8 tocopherols that make up "vitamin E"; pictured at right) into a novel compound with about 90-fold greater antioxidant activity. Even if the new compound does not prove biologically useful, it will still probably find a home in the manufacture of oxidation sensitive products like plastics, rubber, lubricants and cosmetics. (image from Wikipedia.de)


growth inhibition of Micrococcus luteus by Penicillium notatum Potential new antibiotics: chemists at the University of Illinois at Urbana-Champaign have demonstrated that a single enzyme is capable of processing the precursor LctA all the way to the lantibiotic lacticin 481 (abstract from Science vol. 303 pp. 679-81 here). Lantibiotics are small secreted microbicidal peptides that contain the modified amino acid lanthionine, and are particularly attractive as antibacterial agents because they inhibit cell wall synthesis and disrupt the cell membrane. This dual attack makes the development of resistance less likely than with agents that have a single target; for instance, the lantibiotic nisin has been used as a food preservative for more than 50 years in more than 40 countries without resistance related problems. Nisin is produced by certain strains of Lactococcus lactis, occurs naturally in a variety of cheeses and is classified GRAS (generally recognised as safe) by the USFDA. What's cool about this is that the biosynthesis of most antibiotics is so complex that it is virtually impossible to tweak it, but this system offers the possiblity of designer lantibiotics. By modifying LctA or offering other substrates to LctM, we may be able to generate a whole range of new lantibiotics. (The image, from The Microbial World, is just for decoration, and actually shows growth inhibition of Micrococcus luteus by Penicillium notatum.)


bdello.jpg Killer bugs: but not from Outer Space. Bdellovibrio are bacterial predators which actively hunt and kill other bacteria. They are chemotactic, meaning that they can follow concentration gradients of substances likely to lead to prey, and have an impressive arsenal of lytic enzymes with which to enter the target cell and then, essentially, eat it from the inside. Researchers at the Max Planck Institute for Developmental Biology have sequenced the entire genome of Bdellovibrio bacteriovorus, and are looking forward to a smorgasbord of novel enzymatic activities. From the press release:

The researchers will attempt to identify the targets in the prey cell that have proven to be successful points of attack in this million-year-old prey-predator relationship. The lytic enzymes acting on cellular systems that are not targeted by conventional chemical antibiotics are thereby especially interesting.

Far reaching anti-microbial strategies aim at using Bdellovibrio as a "living antibiotic". This seems feasible, as Bdellovibrio is not capable of infecting eukaryotic cells, in particular mammalian cells. Moreover, it was shown in animal experiments that Bdellovibrio only has a weakly immunogenic surface, which does not produce serious life threatening reactions in test animals. These attributes, together with the facts that certain Bdellovibrio strains show a very narrow prey spectrum and are capable of penetrating the same tissues as many human pathogens, gives promise to the development of novel anti-microbial strategies.

The photomicrograph, which I swiped from here, shows B. bacteriovorus (I circled a couple) attacking Spirillum serpens (arrow). The white bar shows 1 millionth of a meter.


reversine.jpg De-differentiation of adult cells is an alternative to the use of embryonic stem cells as a source of pluripotent cells that could be induced to form specific tissues in order to heal wounds, replace organs, and so on. Researchers at the Scripps Institute have used a library screening approach to look for small molecules (read: drugs) which can reverse muscle cell differentiation and allow re-differentiation along a bone cell lineage. While many questions remain, they have come up with a compound which they call "reversine" (pictured at left; pic from J. Am. Chem. Soc. vol. 126 pp. 410 -411) which appears to have the properties they are looking for.


xrayhelix.jpg Computer program speeds up x-ray data analysis:

Scientists are finding a computer program called Elves to be a nearly magical solution to the tedious and time-consuming task of determining the 3-D shape of proteins ... the first time anyone has reported a computer generating a protein structure by itself ... Elves decreases the time and training needed for researchers to interpret X-ray crystallographic data
The big deal here is that 3-D protein structures are the keys to solving an enormous range of biological puzzles, particularly those involving drug design, and this program has made the time from x-ray data to solved structure much shorter (good primers on x-ray crystallography here and here). That's good news not only in the immediate time-saving sense but also in the larger sense that it enables meta-analysis. By reducing analysis times from days/weeks to minutes, the new software will enable side-by-side analysis of, and comparisons between, much larger data sets. For instance,
Holton is taking a second look at X-ray diffraction data that other scientists have given up working on. He hopes to find out what characterizes the nine out of 10 data sets that fail to produce good structural data.
The image at right shows x-ray crystallographic data of considerable historical impact and interest: it was collected by Dr Rosalind Franklin in 1952 and from it was deduced the double-helical structure of DNA. (Incidentally, if you're interested in that famous story, rather than listen to that egregious prick Watson, read this excellent version told from the perspective of Linus Pauling.)

science | sennoma | 04 Feb, 2004 |

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