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Freedom to meet - cuts both ways
46
T1BS - February 1983
Letters to the Editor Why are enzymes so large? sIR: The almost rhetorical question 'why are enzymes so big?', which was put by D. B. Kell in T1BS (1982) Vol. 7, Oct., p. 351, is certainly not answered fully and satisfactorily by 'because they may act as energy funnels'. One should realize that the extensiveness of the catalyst outside the active centre proper affords an opportunity of various kinds of non-specific enzyme-substrate interactions taking place, which may lead to enhanced catalytic efficiency. Permit me to demonstrate this by quoting a few examples. 1. The elaborate computations by Chou et al. ~'2 have shown that the Van der Waals a~action between the enzyme and its substrate outside the active centre may result in the substrate being trapped and accumulated on the enzyme surface. As a consequence, the superficial diffusion of the substrate towards 'the sink' is increased to the extent of restoring the effect of the orientational constraint in the kinetics. In fact, Chou's catalytic model closely resembles the 'sliding' models proposed earlier by Richter and Eigen 3 and by Berg et al. 4 to account for the rate of repressor--operator reaction in E. coli lac DNA. In the latter
case the trapping potential is assumed to be electrostatic. 2. Electrostatic interactions between the enzyme and its substrate beyond the active centre have also been supposed to contribute to the rate of some proteolysis reactions. Thus the helix dipole involved in the catalytic mechanism of papain~ extends well beyond the immediate surroundings of the enzyme's active centre. A further example is afforded by the specific splitting of the bond Phe (105)-Met (106) in K-cassein by milk-clotting chymosin'~'7. In this case it can be shown that the preference of the enzyme for this particular bond is connected with the formation of salt linkages between the catalyst and its substrate outside the active centre proper. Depending on the ionic strength, these linkages can stabilize a particular enzyme-substrate configuration, as a result of which the splitting of the Phe-Met bond in K-casein takes priority over the non-specific splitting of other bonds. The above examples may serve to demonstrate that the extensiveness of the enzyme molecule beyond the active site is of great consequence, because it may
Freedom to meet - c u t s both ways SIR: In the October issue [TIBS (1982) Vol. 7, pp. 351], Professors Wood and Whelan have emphatically restated the position that there be unrestricted access to meetings such as the International Congress of Biochemistry for bona fide scientists. This is a position which has my strong support; I am in favor of open exchanges of all kinds. A corollary to this position is that I am also concerned that many Soviet scientists have suffered interruption of their careers as a result of political and religious beliefs. In the case of Academician Ovchinnikov, who was denied access to the Perth meeting, I have distinctly mixed feelings. I had heard him lecture in Pittsburgh (1967) and later met him at dinner in a private home. He was clearly a talented scientist; perhaps nai'vely, I gained the impression that he was not deeply involved in the politics of the Soviet Union. I was, therefore, considerably distressed to fred that he was a signatory of a profoundly 'anti-Sakharov' letter in 1973. This letter, signed by 40 Soviet academicians (five of them foreign
associates of the U.S. National Academy of Sciences) was published in Pravda (29 August 1973); a translation appeared in Science (Vol. 182, p. 334, 1973). The thrust of the letter was clear. By meeting with Western journalists in his apartment on 21 August of that year, Sakharov had defamed the honor and dignity of a Soviet scientist. He had actively identified himself with the most reactionary, imperialistic circles, and had defamed the government and the foreign and internal politics of the 'Soviet Union. He had become an instrument of hostile propaganda against the
induce non-specific enzyme-substrate interactions. In particular, Van der Waals and electrostatic dipole 8 interactions will increase with the size of the enzyme molecule. in writing this letter I do not challenge Kell's ideas about enzymes acting as energy funnels and I share his pessimistic feelings on the outcome of biomimetic experiments.
References 1 Kuo-chen Chou and Shoo-ping Jiang (1974) Sci. Sin. XVll, 664--68(/ 2 Cuo-Ping Zhou, Tse-Tsai Li and Kuo-chen Chou (1981) Biophys. Chem. 14, 277-281 3 Richter, P. H. and Eigen, M. (1974) Biophys. ('hem. 2, 255-263 4 Berg, Otto G., Winter, R. B. and yon Hippel, P. H. (1982) Trends Biochem. Sci. 7, 52-55 5 van Duijnen, P. Th., Thole, B. T. and Hol, W. G. J. (1979) Biophys. Chem. 9,273-280 6 Payens, T. A. and Both, P. in Bioelectrochemistry: Ions, Surfaces, Membranes (Blank, M., ed.), Adv. Chem. Ser. (1980) 188, 129-141 7 Visser, S., van Rooijen, P. J. and Slangen, K. J. (1980) Eur. J. Biochem. 108,415-421 8 Koppenol, W. H. (1980) Biophys. J. 29, 49.3-508 T. A. J. PAYENS
The Netherlands Institute Research, P.O. Box 20, 6710 BA, Ede, The Netherlands.
for
Dairy
Soviet Union and other socialist countries, etc. The subsequent fate of Sakharov is of course well known; one can only conclude that this letter was a contributing factor. The letter to Pravda concluded by hoping that'Academician Sakharov ponders on his actions'. I also hope that Academician Ovchinnikov may likewise ponder his actions. Perhaps he might then share my feeling that 'Do as you would be done by' is an appropriate maxim. RONALD BENTLEY
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, U.S.A.
Freedom to meet - a question of impartiality SIR: The IUB Executive Committee and General Assembly were quite right in protesting to the Australian Prime Minister and Foreign Minister about the refusal to grant entry visas to Academician Ovchinnikov and Professor S. S. Debov of the Soviet Union to participate in the 12th International Congress of Biochemistry in Perth.
The principle of free circulation of and discussion by scientists of all countries must not be violated for whatever political reason. The IUB resolution and the comments on the Congress by Professors Wood and Whelan [TIBS (1982) Vol. 7, Oct., p. 351 ] leave much to be desired. Why, for
T1BS - February 1983
Letters to the Editor Why are enzymes so large? sIR: The almost rhetorical question 'why are enzymes so big?', which was put by D. B. Kell in T1BS (1982) Vol. 7, Oct., p. 351, is certainly not answered fully and satisfactorily by 'because they may act as energy funnels'. One should realize that the extensiveness of the catalyst outside the active centre proper affords an opportunity of various kinds of non-specific enzyme-substrate interactions taking place, which may lead to enhanced catalytic efficiency. Permit me to demonstrate this by quoting a few examples. 1. The elaborate computations by Chou et al. ~'2 have shown that the Van der Waals a~action between the enzyme and its substrate outside the active centre may result in the substrate being trapped and accumulated on the enzyme surface. As a consequence, the superficial diffusion of the substrate towards 'the sink' is increased to the extent of restoring the effect of the orientational constraint in the kinetics. In fact, Chou's catalytic model closely resembles the 'sliding' models proposed earlier by Richter and Eigen 3 and by Berg et al. 4 to account for the rate of repressor--operator reaction in E. coli lac DNA. In the latter
case the trapping potential is assumed to be electrostatic. 2. Electrostatic interactions between the enzyme and its substrate beyond the active centre have also been supposed to contribute to the rate of some proteolysis reactions. Thus the helix dipole involved in the catalytic mechanism of papain~ extends well beyond the immediate surroundings of the enzyme's active centre. A further example is afforded by the specific splitting of the bond Phe (105)-Met (106) in K-cassein by milk-clotting chymosin'~'7. In this case it can be shown that the preference of the enzyme for this particular bond is connected with the formation of salt linkages between the catalyst and its substrate outside the active centre proper. Depending on the ionic strength, these linkages can stabilize a particular enzyme-substrate configuration, as a result of which the splitting of the Phe-Met bond in K-casein takes priority over the non-specific splitting of other bonds. The above examples may serve to demonstrate that the extensiveness of the enzyme molecule beyond the active site is of great consequence, because it may
Freedom to meet - c u t s both ways SIR: In the October issue [TIBS (1982) Vol. 7, pp. 351], Professors Wood and Whelan have emphatically restated the position that there be unrestricted access to meetings such as the International Congress of Biochemistry for bona fide scientists. This is a position which has my strong support; I am in favor of open exchanges of all kinds. A corollary to this position is that I am also concerned that many Soviet scientists have suffered interruption of their careers as a result of political and religious beliefs. In the case of Academician Ovchinnikov, who was denied access to the Perth meeting, I have distinctly mixed feelings. I had heard him lecture in Pittsburgh (1967) and later met him at dinner in a private home. He was clearly a talented scientist; perhaps nai'vely, I gained the impression that he was not deeply involved in the politics of the Soviet Union. I was, therefore, considerably distressed to fred that he was a signatory of a profoundly 'anti-Sakharov' letter in 1973. This letter, signed by 40 Soviet academicians (five of them foreign
associates of the U.S. National Academy of Sciences) was published in Pravda (29 August 1973); a translation appeared in Science (Vol. 182, p. 334, 1973). The thrust of the letter was clear. By meeting with Western journalists in his apartment on 21 August of that year, Sakharov had defamed the honor and dignity of a Soviet scientist. He had actively identified himself with the most reactionary, imperialistic circles, and had defamed the government and the foreign and internal politics of the 'Soviet Union. He had become an instrument of hostile propaganda against the
induce non-specific enzyme-substrate interactions. In particular, Van der Waals and electrostatic dipole 8 interactions will increase with the size of the enzyme molecule. in writing this letter I do not challenge Kell's ideas about enzymes acting as energy funnels and I share his pessimistic feelings on the outcome of biomimetic experiments.
References 1 Kuo-chen Chou and Shoo-ping Jiang (1974) Sci. Sin. XVll, 664--68(/ 2 Cuo-Ping Zhou, Tse-Tsai Li and Kuo-chen Chou (1981) Biophys. Chem. 14, 277-281 3 Richter, P. H. and Eigen, M. (1974) Biophys. ('hem. 2, 255-263 4 Berg, Otto G., Winter, R. B. and yon Hippel, P. H. (1982) Trends Biochem. Sci. 7, 52-55 5 van Duijnen, P. Th., Thole, B. T. and Hol, W. G. J. (1979) Biophys. Chem. 9,273-280 6 Payens, T. A. and Both, P. in Bioelectrochemistry: Ions, Surfaces, Membranes (Blank, M., ed.), Adv. Chem. Ser. (1980) 188, 129-141 7 Visser, S., van Rooijen, P. J. and Slangen, K. J. (1980) Eur. J. Biochem. 108,415-421 8 Koppenol, W. H. (1980) Biophys. J. 29, 49.3-508 T. A. J. PAYENS
The Netherlands Institute Research, P.O. Box 20, 6710 BA, Ede, The Netherlands.
for
Dairy
Soviet Union and other socialist countries, etc. The subsequent fate of Sakharov is of course well known; one can only conclude that this letter was a contributing factor. The letter to Pravda concluded by hoping that'Academician Sakharov ponders on his actions'. I also hope that Academician Ovchinnikov may likewise ponder his actions. Perhaps he might then share my feeling that 'Do as you would be done by' is an appropriate maxim. RONALD BENTLEY
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, U.S.A.
Freedom to meet - a question of impartiality SIR: The IUB Executive Committee and General Assembly were quite right in protesting to the Australian Prime Minister and Foreign Minister about the refusal to grant entry visas to Academician Ovchinnikov and Professor S. S. Debov of the Soviet Union to participate in the 12th International Congress of Biochemistry in Perth.
The principle of free circulation of and discussion by scientists of all countries must not be violated for whatever political reason. The IUB resolution and the comments on the Congress by Professors Wood and Whelan [TIBS (1982) Vol. 7, Oct., p. 351 ] leave much to be desired. Why, for