Potters M Ben, Solow Barbara T, Bischoff Kenneth M, Graham David E, Lower Brian H, Helm Richard, Kennelly Peter J
Department of Biochemistry and Virginia Institute for Genomics, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA.
J Bacteriol. 2003 Apr;185(7):2112-21. doi: 10.1128/JB.185.7.2112-2121.2003.
When soluble extracts of the extreme acidothermophilic archaeon Sulfolobus solfataricus were incubated with [gamma-(32)P]ATP, several proteins were radiolabeled. One of the more prominent of these, which migrated with a mass of approximately 46 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), was purified by column chromatography and SDS-PAGE and subjected to amino acid sequence analysis via both the Edman technique and mass spectroscopy. The best match to the partial sequence obtained was the potential polypeptide product of open reading frame sso0417, whose DNA-derived amino acid sequence displayed many features reminiscent of the 2,3-diphosphoglycerate-independent phosphoglycerate (PGA) mutases [iPGMs]. Open reading frame sso0417 was therefore cloned, and its protein product was expressed in Escherichia coli. Assays of its catalytic capabilities revealed that the protein was a moderately effective PGA mutase that also exhibited low levels of phosphohydrolase activity. PGA mutase activity was dependent upon the presence of divalent metal ions such as Co(2+) or Mn(2+). The recombinant protein underwent autophosphorylation when incubated with either [gamma-(32)P]ATP or [gamma-(32)P]GTP. The site of phosphorylation was identified as Ser(59), which corresponds to the catalytically essential serine residue in bacterial and eucaryal iPGMs. The phosphoenzyme intermediate behaved in a chemically and kinetically competent manner. Incubation of the (32)P-labeled phosphoenzyme with 3-PGA resulted in the disappearance of radioactive phosphate and the concomitant appearance of (32)P-labeled PGA at rates comparable to those measured in steady-state assays of PGA mutase activity.
将嗜热嗜酸古菌嗜热栖热菌(Sulfolobus solfataricus)的可溶性提取物与[γ-(32)P]ATP一起温育时,有几种蛋白质被放射性标记。其中较为突出的一种蛋白质,在十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)上迁移时的质量约为46 kDa,通过柱色谱和SDS-PAGE进行纯化,并通过埃德曼技术和质谱进行氨基酸序列分析。与所得部分序列最匹配的是开放阅读框sso0417的潜在多肽产物,其DNA衍生的氨基酸序列显示出许多让人联想到不依赖2,3-二磷酸甘油酸的磷酸甘油酸(PGA)变位酶[iPGMs]的特征。因此,克隆了开放阅读框sso0417,并在大肠杆菌中表达了其蛋白质产物。对其催化能力的测定表明,该蛋白质是一种中等效力的PGA变位酶,也表现出低水平的磷酸水解酶活性。PGA变位酶活性依赖于二价金属离子如Co(2+)或Mn(2+)的存在。当与[γ-(32)P]ATP或[γ-(32)P]GTP一起温育时,重组蛋白会发生自磷酸化。磷酸化位点被确定为Ser(59),它对应于细菌和真核生物iPGMs中催化必需的丝氨酸残基。磷酸酶中间体在化学和动力学上表现出活性。将(32)P标记的磷酸酶与3-PGA一起温育,导致放射性磷酸盐消失,并同时出现(32)P标记的PGA,其速率与PGA变位酶活性稳态测定中测得的速率相当。