Inhibition of arylesterase by aliphatic alcohols

被引:19
作者
Debord, J
Dantonine, T
Bollinger, JC
Abraham, MH
Verneuil, B
Merle, L
机构
[1] Serv Pharmacol Toxicol, F-87042 Limoges, France
[2] Hop Dupuytren, Serv Nephrol, F-87042 Limoges, France
[3] Fac Sci, Chim Analyt Lab, F-87060 Limoges, France
[4] Univ London Univ Coll, Dept Chem, London WC1H 0AJ, England
[5] Inst Univ technol, Lab Genie Enzymat & Biovalorisat, F-87065 Limoges, France
关键词
arylesterase; paraoxonase; alcohols; inhibition; structure-activity relationships;
D O I
10.1016/S0009-2797(98)00018-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The inhibition of arylesterase (EC 3.1.8.1) by 11 aliphatic alcohols tone to seven carbon atoms) was studied in blood serum from healthy donors. Inhibition curves were described by the Hill equation, with a Hill coefficient (n) close to unity, except for some alcohols, mainly the lowest. The inhibiting activity of the alcohols was highly dependent on their structure, since the C-50 values covered about three orders of magnitude. The least active compound was methanol (C-50 approximate to 1 M) and the most active was heptanol (C-50 approximate to 7.4 x 10(-4) M). The A and B isozymes (differing by the amino acid at position 191)had similar inhibition parameters with the alcohols tested. Quantitative structure-activity relationships were computed with either the experimental solvation parameters of Abraham [6] or the theoretical parameters of Wilson and Famini [11]. Both methods gave similar results, with a slight advantage to the empirical parameters in terms of simplicity and statistical significance. The two main determinants of inhibition were identified as molecular volume and lack of polarity. The effect of volume was non-linear, tending to a maximum when the length of the alcohol increased. For a given number of carbon atoms, the best inhibitor was the least polar compound. These results point to a binding site consisting mainly of nonpolar aliphatic amino acids, and located in the depth of the protein molecule. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.
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页码:105 / 115
页数:11
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