Guo Youzhong, Qiu Weihua, Roche Thomas E, Hackert Marvin L
Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA 23298, USA.
Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS 66506, USA.
Acta Crystallogr F Struct Biol Commun. 2020 Jul 1;76(Pt 7):292-301. doi: 10.1107/S2053230X20007943.
Mammalian pyruvate dehydrogenase (PDH) activity is tightly regulated by phosphorylation and dephosphorylation, which is catalyzed by PDH kinase isomers and PDH phosphatase isomers, respectively. PDH phosphatase isomer 1 (PDP1) is a heterodimer consisting of a catalytic subunit (PDP1c) and a regulatory subunit (PDP1r). Here, the crystal structure of bovine PDP1c determined at 2.1 Å resolution is reported. The crystals belonged to space group P321, with unit-cell parameters a = b = 75.3, c = 173.2 Å. The structure was solved by molecular-replacement methods and refined to a final R factor of 21.9% (R = 24.7%). The final model consists of 402 of a possible 467 amino-acid residues of the PDP1c monomer, two Mn ions in the active site, an additional Mn ion coordinated by His410 and His414, two MnSO ion pairs at special positions near the crystallographic twofold symmetry axis and 226 water molecules. Several new features of the PDP1c structure are revealed. The requirements are described and plausible bases are deduced for the interaction of PDP1c with PDP1r and other components of the pyruvate dehydrogenase complex.
哺乳动物丙酮酸脱氢酶（PDH）的活性受到磷酸化和去磷酸化的严格调控，这两种过程分别由PDH激酶异构体和PDH磷酸酶异构体催化。PDH磷酸酶异构体1（PDP1）是一种异二聚体，由一个催化亚基（PDP1c）和一个调节亚基（PDP1r）组成。在此，报道了以2.1 Å分辨率测定的牛PDP1c的晶体结构。晶体属于空间群P321，晶胞参数a = b = 75.3，c = 173.2 Å。通过分子置换法解析了结构，并精修至最终R因子为21.9%（R = 24.7%）。最终模型包含PDP1c单体可能的467个氨基酸残基中的402个、活性位点的两个锰离子、由His410和His414配位的另一个锰离子、在晶体学二重对称轴附近特殊位置的两对硫酸锰离子对以及226个水分子。揭示了PDP1c结构的几个新特征。描述了相关要求，并推导了PDP1c与PDP1r以及丙酮酸脱氢酶复合物其他组分相互作用的合理依据。
