The rational parameterization theorem for multisite post-translational modification systems.
The rational parameterization theorem for multisite post-translational modification systems.
复制标题
多站点翻译后修饰系统的合理参数化定理。
DOI：
10.1016/j.jtbi.2009.09.003
复制
发表时间：
2009-12-21
影响因子：
2
通讯作者：
Gunawardena, Jeremy
中科院分区：
文献类型：
--
作者：
Thomson, Matthew;Gunawardena, Jeremy
蛋白质的翻译后修饰在细胞调控中起着核心作用，但随着位点的增加，底物修饰形式(“修饰形式”)的指数增长阻碍了对它的研究。在这里，我们考虑由质量作用动力学下的翻译后修饰产生的生化网络，允许多个底物，在多个位点上具有不同类型的修饰(磷酸化、甲基化、乙酰化等)，由多个正向和反向酶(总数为L)作用，使用一般的酶机制。这些假设比以前的研究要普遍得多。我们证明了稳态模式浓度是一个代数簇，可以用L游离酶浓度的有理函数来表示，其系数是速率常数的有理函数。这种参数化允许通过求解L代数方程来计算稳态，与模拟数量呈指数级增长的微分方程组相比，这是一个显著的减少。这种复杂性崩溃使我们能够在以前难以处理的背景下进行分析，并导致我们审查的生物学预测。我们的结果为翻译后修饰的系统生物学奠定了基础，并暗示了生化网络和代数几何之间更深层次的联系。
Post-translational modification of proteins plays a central role in cellular regulation but its study has been hampered by the exponential increase in substrate modification forms (“modforms”) with increasing numbers of sites. We consider here biochemical networks arising from post-translational modification under mass-action kinetics, allowing for multiple substrates, having different types of modification (phosphorylation, methylation, acetylation, etc) on multiple sites, acted upon by multiple forward and reverse enzymes (in total number L), using general enzymatic mechanisms. These assumptions are substantially more general than in previous studies. We show that the steady-state modform concentrations constitute an algebraic variety that can be parameterised by rational functions of the L free enzyme concentrations, with coefficients which are rational functions of the rate constants. The parameterisation allows steady states to be calculated by solving L algebraic equations, a dramatic reduction compared to simulating an exponentially large number of differential equations. This complexity collapse enables analysis in contexts that were previously intractable and leads to biological predictions that we review. Our results lay a foundation for the systems biology of post-translational modification and suggest deeper connections between biochemical networks and algebraic geometry.
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DOI：
10.1073/pnas.0308265100
发表时间：
2004-02-17
影响因子：
11.1
作者：
Angeli, D;Ferrell, JE;Sontag, ED
通讯作者：
Sontag, ED
影响因子：
4.8
作者：
Ferrell, JE;Bhatt, RR
通讯作者：
Bhatt, RR
影响因子：
0.7
作者：
Gatermann, K;Huber, B
通讯作者：
Huber, B
影响因子：
--
作者：
KING, EL;ALTMAN, C
通讯作者：
ALTMAN, C
DOI：
10.1073/pnas.82.9.3055
发表时间：
1985-01-01
影响因子：
11.1
作者：
LISMAN, JE
通讯作者：
LISMAN, JE