Thekkumkara T J, Pons G, Mitroo S, Jentoft J E, Patel M S
Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
Ann N Y Acad Sci. 1989;573:113-29. doi: 10.1111/j.1749-6632.1989.tb14990.x.
The availability of the primary amino acid sequences of the E2 of PDC, alpha-KGDC and BCKADC from several prokaryotic and eukaryotic species has allowed us to compare the structural aspects of human PDC-E2 with those of the E2 components from the other complexes. The PDC-E2 components from all the species examined so far contain three structurally identifiable regions: the lipoyl-bearing domain, the E3-binding site, and the catalytic domain. The primary structure of the lipoyl-bearing domain shows considerable variation in its size, ranging from one to three repeating units of approximately 110 amino acids, but essentially preserving its function in the E2 components. In contrast, the sizes of the E3-binding site and the catalytic domain of PDC-E2 from several species are essentially similar and show considerable conservation of specific amino acid residues. Obviously, additional studies are warranted to better understand the structure-function relationships of these domains and the evolutionary conservation of PDC-E2 in different species. Similarly, the availability of the primary amino acid sequences of E3 from several prokaryotes and eukaryotes has also permitted comparison of the structural domains of these proteins with that of the known structure of human GR, a flavoprotein member of the pyridine nucleotide-disulfide oxidoreductase family. Four structural domains (FAD, NAD+, central, and interface domains) have been identified in the E3 components. On the basis of the comparison of the secondary structural elements of GR and E3, the core structure of these two proteins are shown to be similar. It is hoped that further analysis of E3 using site-directed mutagenesis and determination of its crystal structure will provide better insight into its structure-function relationships.
来自多个原核生物和真核生物物种的丙酮酸脱氢酶复合体（PDC）、α-酮戊二酸脱氢酶复合体（alpha-KGDC）和支链α-酮酸脱氢酶复合体（BCKADC）E2的一级氨基酸序列，使我们能够比较人类PDC-E2与其他复合体E2组分的结构特征。到目前为止，所有已检测物种的PDC-E2组分都包含三个结构上可识别的区域：含硫辛酰基结构域、E3结合位点和催化结构域。含硫辛酰基结构域的一级结构在大小上有相当大的差异，范围从一个到三个约110个氨基酸的重复单元，但在E2组分中基本保留其功能。相比之下，几种物种的PDC-E2的E3结合位点和催化结构域的大小基本相似，并且特定氨基酸残基有相当程度的保守性。显然，需要进行更多研究以更好地理解这些结构域的结构-功能关系以及不同物种中PDC-E2的进化保守性。同样，来自几种原核生物和真核生物的E3一级氨基酸序列的可得性，也使得能够将这些蛋白质的结构域与已知结构的人类GR（吡啶核苷酸-二硫化物氧化还原酶家族的黄素蛋白成员）的结构域进行比较。在E3组分中已鉴定出四个结构域（FAD、NAD+、中央和界面结构域）。基于GR和E3二级结构元件的比较，显示这两种蛋白质的核心结构相似。希望使用定点诱变对E3进行进一步分析并确定其晶体结构，将能更好地洞察其结构-功能关系。
