Aldolases Utilize Different Oligomeric States To Preserve Their Functional Dynamics.
Aldolases Utilize Different Oligomeric States To Preserve Their Functional Dynamics.
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DOI：
10.1021/acs.biochem.5b00042
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发表时间：
2015-06-09
期刊：
影响因子：
2.9
通讯作者：
Jernigan RL
中科院分区：
文献类型：
--
作者：
Katebi AR;Jernigan RL
醛缩酶是糖酵解途径中的必需酶，并且催化将果糖/塔格糖1，6-二磷酸裂解成二羟丙酮磷酸和甘油醛3-磷酸的反应。为了确定醛缩酶运动如何与其催化过程相关，我们通过模拟研究了三种不同的II类醛缩酶结构的动力学。采用粗粒度弹性网络正态模分析方法研究了大肠杆菌果糖1，6-二磷酸醛缩酶、大肠杆菌塔格糖1，6-二磷酸醛缩酶和水生栖热菌果糖1，6-二磷酸醛缩酶的动力学行为，并比较了它们在不同寡聚态下的运动。第一个是二聚体，第二个和第三个是四聚体。我们的分析表明，寡聚化不仅稳定了醛缩酶的结构，减少了亚基界面的波动，它进一步使酶实现所需的动力学功能循环。这些环在功能性寡聚体状态下的基本移动性可以促进酶机制-在开放状态下的底物募集，使催化残基在闭合结合状态下形成其所需的构型，并移回开放状态以释放催化产物并重新定位酶用于其下一个催化循环。这些发现表明，为了保持其催化机制，具有不同寡聚体状态的醛缩酶之间的醛缩酶的全局运动是保守的。粗粒度的方法允许前所未有的视图中的结构动态变化，以及这些如何与关键的催化结构稳定性至关重要。这些结果得到了许多先前研究的实验结果的支持。
Aldolases are essential enzymes in the glycolysis pathway and catalyze the reaction cleaving fructose/tagatose 1,6-bisphosphate into dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. To determine how the aldolase motions relate to its catalytic process, we studied the dynamics of three different class II aldolase structures through simulations. We employed coarse-grained elastic network normal mode analyses to investigate the dynamics of E.coli fructose 1,6-bisphosphate aldolase, E.coli tagatose 1,6-bisphosphate aldolase, and T.aquaticus fructose 1,6-bisphosphate aldolase, and compared their motions in different oligomeric states. The first one is a dimer, and the second and third ones are tetramers. Our analyses suggest that oligomerization not only stabilizes the aldolase structures, showing reduced fluctuations at the subunit interfaces, it further enables the enzyme to achieve the required dynamics for its functional loops. The essential mobility of these loops in the functional oligomeric states can facilitate the enzymatic mechanism – substrate recruitment in the open state, bringing the catalytic residues into their required configuration in the closed bound state, and moving back to the open state to release the catalytic products and re-positioning the enzyme for its next catalytic cycle. These findings suggest that the aldolase global motions are conserved among aldolases having different oligomeric states in order to preserve its catalytic mechanism. The coarse-grained approaches taken permit an unprecedented view of the changes in the structural dynamics and how these relate to the critical structural stabilities essential for catalysis. The results are supported by experimental findings from many previous studies.
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DOI：
10.1016/s1359-0278(97)00024-2
发表时间：
1997-01-01
期刊：
FOLDING & DESIGN
影响因子：
--
作者：
Bahar, I;Atilgan, AR;Erman, B
通讯作者：
Erman, B
影响因子：
3.1
作者：
EYRISCH, O;SINERIUS, G;FESSNER, WD
通讯作者：
FESSNER, WD
影响因子：
2
作者：
Miteva, M;Alexov, E;Atanasov, B
通讯作者：
Atanasov, B
催化环运动与酶全球动力学之间的耦合。
影响因子：
4.3
作者：
Kurkcuoglu Z;Bakan A;Kocaman D;Bahar I;Doruker P
通讯作者：
Doruker P
影响因子：
2.9
作者：
Bahar, I;Erman, B;Jernigan, RL
通讯作者：
Jernigan, RL