NEWS OF THE WEEK
HOUSE PASSES ENERGY BILLS LEGISLATION: Renewable energy would get boost through House bills
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N A RARE SATURDAY vote on Aug. 4, the House cleared two energy-related bills, one emphasizing renewable energy and efficiency and the other fo cusing on energy taxes by eliminating tax breaks for oil and gas production and adding tax support for renew able energy. More than a month earlier, the Senate passed its en ergy bill. The two bills have differences, which Congress will try to resolve in conference committee debate when members return in September from the August recess. The conference is likely to be difficult but lively. Among the dissimilarities, the House bill would require that, by 2020, utilities generate 15% of their electricity from renewable sources—wind, solar, and hydropower. Sen. Jeff Bingaman (D-N.M.) pushed un successfully for such a "renewable portfolio standard" in the Senate but could not overcome objections by
NOVEL ANTIBIOTIC MECHANISM STRUCTURAL BIOLOGY: Picture of lactivicin bound to its target may aid fight against drug-resistant bacteria
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RYSTAL STRUCTURES of a long-neglected antibiotic may provide a starting point for more effective drugs against bacteria resistant to anti biotics such as penicillin. The antibiotic is lactivicin, and crystal structures of it bound to penicillin-binding protein (PBP) reveal how it interacts with its target. Lactivicin is unusual because it is the only known naturally occurring PBP inhibitor that doesn't contain a β-lactam (a four-membered cyclic amide), a structural feature that is key to the biological activity of the group of antibiotics that includes penicillin and cephalosporins. Lactivicin was discovered more than 20 years ago, but it has languished because of its poor potency. A Eu ropean team led by Christopher J. Schofield at the Uni versity of Oxford and Andréa Dessen at the Institute of Structural Biology, in Grenoble, France, hopes to revive interest in its analogs. Many drug-resistant bacteria have mutations in their PBPs that allow them to evade β-lactams. Instead of a β-lactam ring, lactivicin and its derivatives contain
Sen. Pete V. Domenici (R-N.M.) and others. Bingaman and Domenici will continue their disagreement in con ference, as both will be at the conference table. Another hot area is auto efficiency standards, which are in the Senate bill but not in the House bill, primar ily due to strong objections from Rep. John D. Dingell (D-Mich.). Although other House members are likely to try to add auto efficiency to the conference bill, Dingell, as chair of the House Energy & Commerce Committee, is sure to be there to try to bat down their amendments. In addition, the Senate bill includes sup port for cellulosic ethanol, and the House bill does not. Ethanol has powerful congres sional supporters who are likely to try to include such provisions during conference. Although the House bill's bent for re newable energy enjoys support from envi ronmental groups and renewable energy advocates, the American Chemistry Council and other industry organizations bemoan provisions removing incentives for greater natural gas and oil production and blocking access to potential gas fields. Energy Secretary Samuel W. Bodman warned that the President will veto the bill if the final version con tains no production incentives.—JEFF JOHNSON
separate cycloserine andy-lactone (a five-membered cyclic ester) rings. This structural difference allows lactivicins to recognize and inhibit mutated PBPs from resistant bacteria. Schofield, Dessen, and coworkers have now ob tained crystal structures of lactivicin and a more potent analog, phenoxyacetyl-lactivicin, each complexed with the PBP from Streptococcus pneumoniae (Nat. Chem. Biol, DOI: 10.1038/ nchembio.2007.21). In both com plexes, both of the lactivicin rings are open, and the antibiotics covalently bind to a serine in the protein. The researchers were surprised by "how close in struc ture the resultant inhibitor complex was to the analogous complex formed by reaction with a β-lactam," Schofield says. "The work is a beautiful example of how chemistry and structural biology can converge in finding answers to important biomedical problems," says Shahriar Mobashery, an antibiotic resistance expert at the University of Notre Dame. "The mechanism is novel, and it might stimulate further study in the system by others to exploit it fully." Schofield hopes that the structure will inspire a re newed interest in this neglected family of antibiotics. "This is by no means a solution to the problem of anti biotic resistance," he says. But "the structure may pro vide ideas to develop compounds that don't suffer from the same problems of resistance."—CELIA ARNAUD
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AUGUST 13, 2007
Phenoxyacetyllactivicin (electron density shown in green) complexed with penicillinbinding protein.
