possible to design molecules to inhibit specific forms of the enzyme, Ignarro says, thereby affecting some of NO's many biological functions without disrupting them all. "We've shone a light on one part of this very interesting enzyme system," Tainer says, "and we now know quite a bit about the heme environment" where NO is cleaved from L-arginine. "It really looks to us like the arginine itself is facilitating the reaction," he says, noting that this is a controversial explanation of how the enzyme might operate. The structure "suggests the kind of experiments to do to verify this or disprove it." Rebecca Rawls
Hemoglobin, center left, rests like the ball in a catcher's mitt in the catalytic site of nitric oxide synthase.
through walls, that can 'toast' its enemies," says crystallographer John A. Tainer of Scripps Research Institute, La Jolla, Calif. "It's an oxidant for pathogens and it's a chemical signal, and those two things are regulated by one enzyme that, strangely enough, makes NO by starting with arginine. It really catches your imagination." Along with biochemist Dennis J. Stuehr at the Cleveland Clinic in Ohio, Tainer led the team that solved the structure [Science, 278, 425 (1997)]. Key to the solution, Tainer says, was the work of former graduate student Brian R. Crane (now at California Institute of Technology) and Scripps scientific associate Andrew S. Arvai. "This is an outstanding achievement, the culmination of an immense amount of work," says Jack L. Lancaster, professor of medicine at Louisiana State University Medical Center in New Orleans and a researcher on NO. "One of the major black boxes in this field has been how this complex enzyme makes NO from L-arginine, dioxygen, and the cofactor nicotineadenine dinucleotide phosphate. Although it was known that the reaction superficially resembles those carried out by the cytochrome P450 class of enzymes, it now becomes clear that NO synthase is its own enzyme," he explains. The structure "is important and informative to those of us working in the field of NO research," says Louis J. Ignarro, professor of molecular pharmacology at the University of California, Los Angeles, School of Medicine. Among other things, the structure suggests that it should be
National Science Board meets in Houston, tackles policy issues The National Science Board (NSB), the governing body of the National Science Foundation, held its first off-site meeting in Houston just over a week ago. The board, which usually meets at NSF headquarters in Arlington, Va., intends to hold at least one meeting a year at another location. The meetings, which will focus on important national science policy topics, are a way of getting input from communities outside the Washington area. In Houston, NSB looked at two topics—a working paper on priorities in government funding of scientific research, and graduate and postgraduate education. The brief working paper finally has been accepted by the group and, after minor editing, probably will be sent to White House science adviser John H. Gibbons for comment. By its next meeting in mid-November, NSB expects to be able to decide about making it public. However, NSB, which has been working on the document for about one and a half years, thought it was nearly done once before (C&EN, Sept. 1, page 12). At Gibbons' request, NSB is looking into the federal role in science and engineering graduate and postgraduate education. Its effort is part of a broader review of the government/university partnership being conducted by the National Science & Technology Council (NSTC). At the Houston meeting, directors from government agencies and nearly a dozen representatives from academe
spoke to the national interest and federal involvement in graduate education, and addressed related needs, issues, and tensions between universities and the government. Among the questions broached were those of funding, infrastructure, and other costs; the status of graduates as students versus employees; diversity and foreign enrollment; and appropriate training and employment. Malcolm Gillis, president of Rice University in Houston, noted that "higher education is receiving perhaps more mixed messages from government today than at any time in the decades-long university/ government partnership." But, he added, "research universities have agonized long and loudly over problems stemming from the external environment, while devoting little more than lip service to problems primarily of our own making. It is time to redress that imbalance." Despite poor local turnout, the presentations prompted much discussion among NSB members and a decision to produce an extensive review of the subject and more prescriptive recommendations. The board is moving quickly to produce a working paper on education in time to meet NSTC's new January 1998 deadline for publication of its report. The report had been due in August (C&EN, March 24, page 34). Ann Thayer
Congress revives chemical accident board Buried in the Environmental Protection Agency's fiscal 1998 appropriation recently approved by Congress is $4 million for an independent chemical accident investigative board. The board was created in 1990, when the Clean Air Act was last amended, but never put into operation. Its fate remains uncertain, despite support from some 80 community, environmental, and labor organizations, and from the governors of West Virginia and New Jersey, the American Institute of Chemical Engineers, and a few chemical companies. President Bill Clinton opposes the board and may use his new line-item veto power to deep-six it once again. Similar in design to the National Transportation Safety Board, the Chemical Safety & Hazard Investigation Board was established to provide an independent assessment of chemical accidents. President OCTOBER 20, 1997 C&EN 13
