Valle Mikel
Structural Biology Unit, Center for Cooperative Research in Biosciences, CIC bioGUNE, 48160, Derio, Spain.
Subcell Biochem. 2017;83:291-322. doi: 10.1007/978-3-319-46503-6_11.
Pyruvate carboxylase is a metabolic enzyme that fuels the tricarboxylic acid cycle with one of its intermediates and also participates in the first step of gluconeogenesis. This large enzyme is multifunctional, and each subunit contains two active sites that catalyze two consecutive reactions that lead to the carboxylation of pyruvate into oxaloacetate, and a binding site for acetyl-CoA, an allosteric regulator of the enzyme. Pyruvate carboxylase oligomers arrange in tetramers and covalently attached biotins mediate the transfer of carboxyl groups between distant active sites. In this chapter, some of the recent findings on pyruvate carboxylase functioning are presented, with special focus on the structural studies of the full length enzyme. The emerging picture reveals large movements of domains that even change the overall quaternary organization of pyruvate carboxylase tetramers during catalysis.
丙酮酸羧化酶是一种代谢酶,它利用三羧酸循环的一种中间产物为该循环供能,同时也参与糖异生的第一步反应。这种大型酶具有多种功能,每个亚基包含两个活性位点,可催化两个连续反应,使丙酮酸羧化生成草酰乙酸,还有一个乙酰辅酶A结合位点,乙酰辅酶A是该酶的变构调节因子。丙酮酸羧化酶寡聚体以四聚体形式排列,共价连接的生物素介导羧基在远距离活性位点之间的转移。在本章中,将介绍一些关于丙酮酸羧化酶功能的最新研究发现,特别关注全长酶的结构研究。新出现的情况表明,在催化过程中,结构域会发生大幅度移动,甚至会改变丙酮酸羧化酶四聚体的整体四级结构。