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Enzyme's mechanism made plain

The hydrogen peroxide-mediated inactivation of protein tyrosinase phosphatase 1B likely proceeds as shown, a new study suggests. PTP1B is a key enzyme in insulin signaling and is a therapeutic target for the treatment of type 2 diabetes. The transformation has been thought striking because amide nitrogens are generally poorly nucleophilic; alternative mechanisms leading to the 3-isothiazolidinone in the inactive form (bottom) have been offered. Now, using a small-molecule model of PTP1B's active site, Kent S. Gates and coworkers at the University of Missouri, Columbia, demonstrate that the reaction can occur as indicated--directly by oxidation of the active-site cysteine thiol (top) to a sulfenic acid followed by cyclization of the amide nitrogen onto the oxidized sulfur residue (J. Am. Chem. Soc. 2005, 127, 10830). The mechanism is difficult to test in a protein system, and the small-molecule model has helped clarify how the unusual transformation takes place, Gates says.

Math-based drug delivery

Molecules that perform Boolean logic calculations can control the binding states of artificial nucleic acids known as aptamers and thus the delivery of drugs or other molecules bound to aptamers. Milan N. Stojanovic and Dmitry M. Kolpashchikov of Columbia University link logic gates made of DNA enzymes with DNA aptamers in a molecular circuit through an oligonucleotide that is both the substrate for the enzyme and a switch for the aptamer's binding states (J. Am. Chem. Soc. 2005, 127, 11348). The DNA enzymes are designed as either an "AND" gate, triggered by the presence of two inputs, or a "NOT" gate, triggered by the absence of one specific input. In either case, when the DNA enzyme cleaves the substrate, the aptamer changes conformation, releasing the bound molecule. The researchers have used such logic gates to control the release from aptamers of malachite green and Taq polymerase, the enzyme used in the polymerase chain reaction.

Neon resolves solar structure discrepancy

A new study of neon abundances in nearby cool, sunlike stars offers a solution to a discrepancy surrounding the interior structure of our own sun. Models describing the sun's interior structure that use recent measurements of light elements such as C, N, O, and Ne are strikingly at odds with the structure known from actual, observed solar seismic activity. The sun's Ne abundance, however, which is usually expressed as a ratio with O, is difficult to measure and remains uncertain. Now, astronomers Jeremy J. Drake at the Harvard-Smithsonian Center for Astrophysics in Cambridge, Mass., and Paola Testa at MIT have calculated Ne/O ratios for other stars, using emission spectra recorded by the Chandra X-ray Observatory. They find Ne/O ratios to be much higher than existing estimates for the sun (Nature 2005, 436, 525). Using a similar Ne/O ratio for the sun brings models of its interior structure back in agreement with solar seismic observations. The results imply that the true solar Ne/O abundance ratio is likely similar to those found in other nearby stars.

Transporter protein analyzed

The first crystal structure of a bacterial protein related to sodium- and chloride-dependent neurotransmitter transporters has been obtained. Neurotransmitter transporters terminate nerve transmission by removing neurotransmitters, such as dopamine and serotonin, from synapses in the brains of higher organisms. Eric Gouaux and coworkers at Columbia University analyzed a bacterial amino acid transporter that is similar to neurotransmitter transporters, especially in its substrate- and sodium-binding sites. The crystal structure reveals the architecture of such proteins, provides new information about their substrate-binding and ion-selectivity properties, and hints at their mechanism of action (Nature, published online July 24, dx.doi.org/10.1038/nature03978). A model of the structure (shown) depicts the protein bound to its substrate (leucine, red) and two sodium ions (yellow). The new findings have potential implications for drug discovery: Malfunction of neurotransmitter transporters is associated with depression, Parkinson's disease, and epilepsy, and the transporters are also known to interact with addictive substances such as cocaine and amphetamine.

Surfactants might tame hurricanes

Since antiquity, sailors have spread oil on the sea to quell storms. "Possibly hurricanes can be similarly prevented or damped by having airplanes deliver fast-decaying, harmless surfactants to the right places on the sea surface," according to University of California, Berkeley, mathematician Alexandre J. Chorin and colleagues. The suggestion is based on their new mathematical model of turbulence and airflow above oceans (Proc. Natl. Acad. Sci. USA 2005, 102, 11148). The model shows that the cloud of spray kicked up by wind over an ocean reduces turbulence and friction in the air above the water. As a result, airflow over the water can pick up speed, accelerating to as much as 200 mph. Without the ocean spray's lubricating effect, winds would top out at a mere 25 mph, according to the mathematicians. They believe that when sailors pour oil on the sea, the oil prevents water droplets from forming, increases turbulent drag, and reduces the intensity of squalls.