Hill coefficients, dose–response curves and allosteric mechanisms

Journal of Chemical Biology

Heino Prinz¹ 

[1] Max-Planck-Institut für molekulare Physiologie, Otto-Hahn-Str. 11, 44227 Dortmund, Germany

关键词: Hill coefficients;    Dose–response curves;    Allosteric mechanisms;    High throughput screening;    Protein denaturation;   

DOI  :  10.1007/s12154-009-0029-3

学科分类：分子生物学，细胞生物学和基因

来源: Springer

【 摘 要 】

Hill coefficients (nH) derived from four parameter logistic fits to dose–response curves were compared to calculated realistic reaction schemes and related to experimental data: (1) Hill coefficients may give information on the number of interacting sites but cannot distinguish between competitive, non-competitive or ortho-, iso-, or allosteric mechanisms. (2) For enzymatic dose–inhibition curves, Hill coefficients smaller than one do not indicate anticooperative binding but show that at least one ternary complex has enzymatic activity. (3) Hill coefficients different from one are proof for multiple ligand binding. The large variations of reported Hill coefficients corresponds to multiple allosteric binding, where induced conformational changes cause loss of the active conformation. Such a denaturation mechanism is in stark contrast to the desired specificity of drugs. The discussion is open.

【 授权许可】

Unknown