Lioliou Efthimia E, Kyriakidis Dimitrios A
Laboratory of Biochemistry, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece.
Microb Cell Fact. 2004 Jun 16;3(1):8. doi: 10.1186/1475-2859-3-8.
This review considers the role of bacterial antizyme in the regulation of polyamine biosynthesis and gives new perspectives on the involvement of antizyme in other significant cellular mechanisms. Antizyme is a protein molecule induced by the end product of the enzymic reaction that it inhibits, in a non-competitive manner. The bacterial ornithine decarboxylase is regulated by nucleotides, phosphorylation and antizyme. The inhibition of ornithine decarboxylase by antizyme can be relieved to different degrees by DNA or by a variety of synthetic nucleic acid polymers, attributed to a specific interaction between nucleic acid and antizyme. Recently, this interplay between bacterial antizyme and nucleic acid was determined by discerning an additional function to antizyme that proved to be the atoC gene product, encoding the response regulator of the bacterial two-component system AtoS-AtoC. The gene located just upstream of atoC encodes the sensor kinase, named AtoS, that modulates AtoC activity. AtoC regulates expression of atoDAEB operon which is involved in short-chain fatty acid metabolism. Antizyme is thus referred to as AtoC, functioning both as a post-translational and transcriptional regulator. Also, the AtoS-AtoC signal transduction system in E. coli has a positive regulatory role on poly-(R)-3-hydroxybutyrate biosynthesis. The properties and gene structural similarities of antizymes from different organisms were compared. It was revealed that conserved domains are present mostly in the C-domain of all antizymes. BLAST analysis of the E. coli antizyme protein (AtoC) showed similarities around 69-58% among proteobacteria, g-proteobacteria, enterobacteria and the thermophilic bacterium Thermus thermophilus. A working hypothesis is proposed for the metabolic role of antizyme (AtoC) describing the significant biological implications of this protein molecule. Whether antizymes exist to other enzymes in different tissues, meeting the criteria discussed in the text remains to be elucidated.
本综述探讨了细菌抗酶在多胺生物合成调控中的作用,并为抗酶参与其他重要细胞机制提供了新的视角。抗酶是一种由其以非竞争性方式抑制的酶促反应终产物诱导产生的蛋白质分子。细菌鸟氨酸脱羧酶受核苷酸、磷酸化和抗酶的调节。抗酶对鸟氨酸脱羧酶的抑制作用可被DNA或多种合成核酸聚合物不同程度地解除,这归因于核酸与抗酶之间的特异性相互作用。最近,通过识别抗酶的另一种功能确定了细菌抗酶与核酸之间的这种相互作用,该功能被证明是atoC基因产物,编码细菌双组分系统AtoS - AtoC的应答调节因子。位于atoC上游的基因编码传感激酶,名为AtoS,它调节AtoC的活性。AtoC调节参与短链脂肪酸代谢的atoDAEB操纵子的表达。因此,抗酶被称为AtoC,兼具翻译后和转录调节因子的功能。此外,大肠杆菌中的AtoS - AtoC信号转导系统对聚(R)-3 - 羟基丁酸酯的生物合成具有正向调节作用。比较了不同生物体抗酶的特性和基因结构相似性。结果表明,保守结构域大多存在于所有抗酶的C结构域中。对大肠杆菌抗酶蛋白(AtoC)的BLAST分析表明,在变形菌门、γ - 变形菌纲、肠杆菌科细菌和嗜热栖热菌之间,其相似性约为69% - 58%。针对抗酶(AtoC)的代谢作用提出了一个工作假说,描述了这种蛋白质分子的重要生物学意义。不同组织中是否存在符合本文所讨论标准的针对其他酶的抗酶仍有待阐明。