The third program, costing $7 billion, is a stepped-up version of the PSAC proposal—the second program. One feature of this program would be a specific mission objective; for example, a manned mission to Mars by some fixed date, say 1985. In the committee's opinion, this kind of program is "a vigorous, expanded space program capable of supporting a manned planetary exploration decision at an early date."
Tariff talks not very promising "Unless some agreement is reached within the next two or three weeks in the Kennedy round of tariff negotiations, we've had it.'' That's the word from a top U.S. trade official just back from Geneva, the scene of the bargaining. He still gives the negotiations a 60/40 chance of success but, he admits with a rueful shake of the head, not many are sharing his mildly optimistic view. Authority to negotiate tariffs in the so-called Kennedy round ends June 30 when the Trade Expansion Act of 1962 expires. However, the practical deadline for action is March 31. The reason is that once major agreements have been reached, it will take about three months to work out the details and get the papers signed. The trade official believes that our trading partners are now convinced that the time for foot dragging is over. In the industrial sector, negotiations on chemical tariffs remain at a standstill. The major stumbling block is whether the U.S. will negotiate on the elimination of the American Selling Price system of customs valuation. This system is applied to benzenoid chemicals. U.S. negotiators still maintain this position on ASP: Any conversion of ASP to the normal valuation system would require special counter concessions; Congress would have to approve such a conversion. The U.S. team has not made a firm offer yet but it is considering sacrificing ASP for adjusted tariff rates in return for elimination of nontariff barriers by the European Economic Community. This whole package would be subject to approval by Congress. Tariff negotiations have also bogged down on pulp and paper, aluminum, steel, and farm products. One bright spot is the feeling that an international agreement on how to define and control dumping is likely to emerge from the sessions. Unless negotiations in the Kennedy round reverse themselves and become a success almost overnight, the outlook is grim. Some people think that if the outlook for success is good near the
time when the Trade Expansion Act is due to expire, Congress will automatically extend the act for 30, 60, or 90 days. However, the trade official believes that Congress will not extend the act under any circumstances. There may be strong support for temporary extension in the House, but he believes that the Senate will firmly oppose any such move. If the Kennedy round fails, the trade official thinks that protectionist sentiment in Congress will rise. As a result, the Administration is likely to ask Congress merely for authority to handle routine trade problems.
S atom changes subtilisin A Northwestern University chemist and his Hungarian coworker have shown that changing a single atom in a massive enzyme molecule can drastically change the enzyme's reactivity and produce an essentially new enzyme. They have found that thiolsubtilisin, a modified enzyme made by replacing an oxygen atom in the active site of the native enzyme subtilisin with an atom of sulfur, shows markedly different properties. In their first detailed report on the reactivity of thiol-subtilisin [Biochemistry, 6, 610 (1967)], NU's Dr. Myron L. Bender and coworker Dr. Laszlo Polgar of the Hungarian Academy of Sciences say that the modified enzyme is much less active than subtilisin in most reactions, although it seems to work by the same mechanism in many of them. In some reactions catalyzed by the native enzyme, thiolsubtilisin will not work. But with reactions involving nucleophiles, the modified enzyme is more active. Thiol-subtilisin has also been made by Dr. D. E. Koshland, Jr., and coworkers at the University of California, Berkeley. Dr. Bender explains that hydrolytic reactions catalyzed by enzymes usually work through formation of an intermediate acyl enzyme. The hydroxyl group of a serine residue or the thiol group of a cysteine residue forms an intermediary bond with the substrate. These two residues, which form the active sites of the enzymes, differ in only one atom—the oxygen in the hydroxyl group of the serine or the sulfur atom of the cysteine. This is the change brought about in making thiolsubtilisin from subtilisin. The preparation of thiol-subtilisin takes three steps: • The native enzyme is reacted with phenylmethanesulfonyl fluoride, which completely activates the enzyme. • T h e phenylmethanesulfonyl group is displaced with thiolacetate ion. • The resulting acetyl-thiol-subtilisin
is allowed to deacylate enzymically. Titration with p-chloromercuribenzoate confirms the presence of the thiol group in the product. Amino acid analysis confirms the cysteine residue. Dr. Bender says the synthesis verifies the usefulness of this relatively simple technique for making other enzymes. It can be applied to any enzyme which, like subtilisin, contains no disulfide bridge. Such bridges would be damaged by the thiolacetate. The NU workers find that the catalytic activity of thiol-subtilisin toward p-nitrophenyl acetate and N-trans-cinnamoylimidazole substrates is significantly lower than that of subtilisin. Also, the modified enzyme apparently shows no activity toward alkyl esters and amide substrates such as N-acetylL-tryptophan methyl ester and N-benzoylarginine amide. Dr. Bender says that this inactivity of thiol-subtilisin toward some substrates affected by the native enzyme may be due to an inherently lower activity of the modified enzyme. However, it may be due to a specificity of the modified enzyme for acylating substrates with good leaving groups such as p-nitrophenyl esters and Nfrans-cinnamoylimidazole. In this specificity, thiol-subtilisin would resemble D-glyceraldehyde-3-phosphatedehydrogenase. This generally lower deacylation activity of thiol-subtilisin, compared with subtilisin, is probably due to the larger sulfur atom which presumably changes the steric structure of the active site, Dr. Bender says. This interferes with the substrate-enzyme fit and retards activity. One reaction in which the modified enzyme is more active involves glycinamide. This nucleophile speeds the deacylation of cinnamoyl-thiolsubtilisin but has no effect on cinnamoyl-subtilisin. Dr. Bender says this would be expected as thiol esters in general react more readily with nitrogen nucleophiles than do the corresponding oxygen esters.
Simazine ups plants' protein Scientists at Michigan State's herbicide physiology laboratory have uncovered what may eventually prove to be an aid to solving some of the food problems of the developing, protein-shy areas of the world. In experiments at their laboratory, the MSU scientists have been able to increase the protein content of several food and forage crops by as much as 80% by treating them with trace amounts of simazine, a herbicide used to control weeds around fruit trees. Dr. S. K. Ries, the MSU horticulturist in charge of the simazine research, FEB. 20, 1967 C&EN
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