Regulation of the structure and activity of pyruvate carboxylase by acetyl CoA.

Regulation of the structure and activity of pyruvate carboxylase by acetyl CoA.
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DOI:
10.1016/j.abb.2011.11.015
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发表时间:
2012-03-15
影响因子:
3.9
通讯作者:
Attwood, Paul V.
Attwood, Paul V.
中科院分区:
生物学3区
文献类型:
--
作者:
Adina-Zada, Abdussalam;Zeczycki, Tonya N.;Attwood, Paul V.

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在这篇综述中,我们研究的变构激活剂,乙酰辅酶A对丙酮酸羧化酶的结构和催化活性的影响。我们描述了乙酰辅酶A的结合如何产生在电子显微镜下可见的酶的四级和三级结构的总体变化。这些变化有助于稳定酶的四聚体结构。乙酰辅酶A激活酶的主要位点是酶的生物素羧化结构域,其中发生ATP切割和生物素辅基的羧化。除了提高反应速率外,乙酰辅酶A还能增强某些底物的结合,尤其是HCO 3 −,并且与辅因子Mg 2+的结合也存在复杂的相互作用。乙酰辅酶A对丙酮酸羧化酶的激活通常是一个协同过程,尽管来自不同生物体的酶所表现出的协同性程度存在很大程度的差异。来自Rhizobium etli和Staphylococcus aureus的丙酮酸羧化酶的X-射线晶体学全酶结构显示了变构乙酰CoA结合结构域位于生物素羧化和羧基转移以及羧基转移和生物素羧基载体蛋白结构域的界面处。
In this review we examine the effects of the allosteric activator, acetyl CoA on both the structure and catalytic activities of pyruvate carboxylase. We describe how the binding of acetyl CoA produces gross changes to the quaternary and tertiary structures of the enzyme that are visible in the electron microscope. These changes serve to stabilize the tetrameric structure of the enzyme. The main locus of activation of the enzyme by acetyl CoA is the biotin carboxylation domain of the enzyme where ATP-cleavage and carboxylation of the biotin prosthetic group occur. As well as enhancing reaction rates, acetyl CoA also enhances the binding of some substrates, especially HCO3−, and there is also a complex interaction with the binding of the cofactor Mg2+. The activation of pyruvate carboxylase by acetyl CoA is generally a cooperative processes, although there is a large degree of variability in the degree of cooperativity exhibited by the enzyme from different organisms. The X-ray crystallographic holoenzyme structures of pyruvate carboxylases from Rhizobium etli and Staphylococcus aureus have shown the allosteric acetyl CoA binding domain to be located at the interfaces of the biotin carboxylation and carboxyl transfer and the carboxyl transfer and biotin carboxyl carrier protein domains.
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