Schläpfer B S, Zuber H
Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule, Zürich, Switzerland.
Gene. 1992 Dec 1;122(1):53-62. doi: 10.1016/0378-1119(92)90031-j.
The structural genes encoding glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 3-phosphoglycerate kinase (PGK) and the N-terminal part of triosephosphate isomerase (TIM) from mesophilic Bacillus megaterium DSM319 have been cloned as a gene cluster (gap operon) by complementation of an Escherichia coli gap amber mutant. Subsequently, the entire tpi gene, encoding TIM, was isolated by colony hybridization using a homologous probe. Nucleotide (nt) sequence analysis revealed an unidentified open reading frame (urf1) of 1029 bp located 50 nt upstream from the start codon of the gap gene. Gene expression from subclones containing different coding regions was studied by enzyme assay and SDS-PAGE. Both GAPDH and TIM are synthesized in transformed E. coli cells, whereas PGK is not. There is no unequivocal evidence for urf1 expression. Two putative promoter sites are present: one 100 nt upstream from urf1 and one 200 nt upstream from the pgk gene. An inverted repeat following the second promoter site is postulated to be involved in the transcriptional regulation of the operon. Each coding region shows a G+C content of 40% attained by the adaptation of the G+C content of the third base in the codon to compensate the G+C content of the first and second bases. The deduced amino acid (aa) sequences of B. megaterium GAPDH, PGK and TIM were compared with those from the thermophilic Bacillus stearothermophilus by antisymmetrical matrices. The detected characteristic thermophilic-mesophilic exchange pattern concerning aa substitutions between hydrophobic-polar and charged-charged residues corresponds to data obtained for thermophilic and mesophilic lactate dehydrogenases (LDH). The determination of the thermostability of these enzymes revealed two regions of stability for B. megaterium TIM at high enzyme concentrations. Heat treatment seems to be responsible for the conversion of two differently active conformations or the induction of a new quaternary structure.
通过对大肠杆菌gap琥珀突变体进行互补,已克隆出嗜温巨大芽孢杆菌DSM319中编码甘油醛-3-磷酸脱氢酶(GAPDH)、3-磷酸甘油酸激酶(PGK)和磷酸丙糖异构酶(TIM)N端部分的结构基因,形成一个基因簇(gap操纵子)。随后,使用同源探针通过菌落杂交分离出编码TIM的完整tpi基因。核苷酸(nt)序列分析显示,在gap基因起始密码子上游50 nt处有一个1029 bp的未鉴定开放阅读框(urf1)。通过酶活性测定和SDS-PAGE研究了包含不同编码区的亚克隆的基因表达。GAPDH和TIM均在转化的大肠杆菌细胞中合成,而PGK则不合成。没有明确证据表明urf1表达。存在两个推定的启动子位点:一个在urf1上游100 nt处,另一个在pgk基因上游200 nt处。推测第二个启动子位点后的反向重复序列参与操纵子的转录调控。每个编码区的G+C含量为40%,通过调整密码子中第三个碱基的G+C含量来补偿第一和第二个碱基的G+C含量。通过反对称矩阵将巨大芽孢杆菌GAPDH、PGK和TIM的推导氨基酸(aa)序列与嗜热嗜热脂肪芽孢杆菌的序列进行了比较。检测到的关于疏水-极性和带电荷-带电荷残基之间氨基酸取代的特征性嗜热-嗜温交换模式与嗜热和嗜温乳酸脱氢酶(LDH)的数据一致。这些酶的热稳定性测定显示,在高酶浓度下,巨大芽孢杆菌TIM有两个稳定区域。热处理似乎导致了两种不同活性构象的转变或诱导了一种新的四级结构。