Ermakov G L, Goldstein B N
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, 142292, Russia.
Biochemistry (Mosc). 1999 Mar;64(3):326-34.
Recent experimental findings on the structural--functional features of pyruvate dehydrogenase phosphatase (PDP) isolated from various sources are compared. Two alternative mechanisms (a and b) of dephosphorylation of the E1 component in the pyruvate dehydrogenase complex (PDC) are discussed: a) the reaction occurs as a result of stochastic collisions of PDP and PDC, and the generation of an enzyme--substrate complex (PDP--E1--PDC) and dephosphorylation of the E1 component occur independently at different PDP binding sites on the PDC core; b) the dephosphorylation is performed simultaneously by a certain number of PDP molecules symmetrically bound on the PDC core. The second mechanism is suggested by the self-assembly theory of multicomponent enzyme systems and can be proved by kinetic experiments. Based on self-assembly principles and data on feasible binding sites of peripheral components of the PDC, the stoichiometry and mutual location of PDP, pyruvate dehydrogenase kinase, and the E1 component on the core of mammalian PDC are postulated to provide optimal functioning of the PDC. Structural mechanisms of stimulation of PDP activity by Ca2+ and polyamines are also discussed.
比较了从不同来源分离得到的丙酮酸脱氢酶磷酸酶（PDP）的结构-功能特征的最新实验发现。讨论了丙酮酸脱氢酶复合物（PDC）中E1组分去磷酸化的两种替代机制（a和b）：a）反应是由于PDP和PDC的随机碰撞而发生的，酶-底物复合物（PDP-E1-PDC）的生成以及E1组分的去磷酸化在PDC核心的不同PDP结合位点独立发生；b）去磷酸化由对称结合在PDC核心上的一定数量的PDP分子同时进行。第二种机制是由多组分酶系统的自组装理论提出的，并且可以通过动力学实验得到证明。基于自组装原理以及关于PDC外围组分可行结合位点的数据，推测了PDP、丙酮酸脱氢酶激酶和E1组分在哺乳动物PDC核心上的化学计量和相互位置，以确保PDC的最佳功能。还讨论了Ca2+和多胺刺激PDP活性的结构机制。
