A kinetic mechanism of the allosteric control of enzyme-coenzyme binding: glutamate dehydrogenase-NADPH-phosphate-acetate-hydrogen ion interactions.
A kinetic mechanism of the allosteric control of enzyme-coenzyme binding: glutamate dehydrogenase-NADPH-phosphate-acetate-hydrogen ion interactions.
复制标题
酶-辅酶结合的变构控制的动力学机制：谷氨酸脱氢酶-NADPH-磷酸盐-乙酸盐-氢离子相互作用。
作者：
S. Pazhanisamy;S. Maniscalco;N. Singh;H. F. Fisher
我们以前的特点是热力学关系，支配牛肝谷氨酸脱氢酶的NADPH的解离和变构控制的机械和生理上的重要过程中的各种效应。我们已经发现，特定阴离子结合的协同占据，而第二变构乙酸盐结合位点的占据破坏了该阴离子结合位点并对抗这些效应（Singh & Fisher，1994）。我们在这里报告的结果瞬态研究的动力学的各种过程中参与这个复杂的平衡。我们发现，唯一的本质上缓慢的步骤是那些NADPH的结合和解离，整个系统的复杂的动力学行为是由于非常快速的平衡结合过程，涉及磷酸盐，乙酸盐，和氢离子，这些离子施加其各种影响的结合过程的动力学通过改变两个动力学显著的反应物种，E和E-NADPH的平衡浓度。NADPH的协会和解离的缓慢的固有速率归因于配体诱导的构象变化，涉及酶的活性位点裂缝的关闭程度的重大改变。
We have previously characterized the thermodynamic relationships which govern the dissociation of NADPH from bovine liver glutamate dehydrogenase and the allosteric control of that mechanically and physiologically important process by a variety of effectors. We have found that the cooperative occupancy of a specific anion binding, while the occupancy of a second allosteric acetate binding site disrupts that anion binding site and opposes those effects (Singh & Fisher, 1994). We report here the results of transient-state studies on the kinetics of the various processes involved in this complex equilibrium. We find that the only intrinsically slow steps are those of NADPH binding and dissociation, that the complex kinetic behavior of the overall system is due solely to very rapid equilibrium binding processes involving phosphate, acetate, and hydrogen ions, and that these ions exert their various effects on the kinetics of the binding process by altering the equilibrium concentrations of the two kinetically significant reactive species, E and E-NADPH. The slow intrinsic rates of NADPH association and dissociation are ascribed to a ligand-induced conformational change involving a major alteration in the degree of closure of the enzyme's active-site cleft.
天冬氨酸 27 在甲氨蝶呤与大肠杆菌二氢叶酸还原酶结合中的作用。
DOI：
--
发表时间：
1988
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Appleman,JR;Howell,EE;Kraut,J;Kühl,M;Blakley,RL
通讯作者：
Blakley,RL
DOI：
10.1016/s0021-9258(18)54109-0
发表时间：
1993-01
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
N. Singh;S. Maniscalco;H. F. Fisher
通讯作者：
N. Singh;S. Maniscalco;H. F. Fisher
DOI：
10.1016/0167-4838(92)90233-4
发表时间：
1992-02-13
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FISHER, HF;MANISCALCO, S;SRINIVASAN, R
通讯作者：
SRINIVASAN, R