Peptidoglycan synthesis in the absence of class A penicillin-binding proteins in Bacillus subtilis
Peptidoglycan synthesis in the absence of class A penicillin-binding proteins in Bacillus subtilis
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DOI：
10.1128/jb.185.4.1423-1431.2003
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发表时间：
2003-02-01
影响因子：
3.2
通讯作者：
Popham, DL
中科院分区：
文献类型：
--
作者：
McPherson, DC;Popham, DL
青霉素结合蛋白(PBPs)催化合成肽聚糖的最终、必要的反应。三种类型的PBPs催化多肽侧链上的反式、内切或羧基肽酶活性。只有A类高分子量多酚清楚地显示了聚合糖链的糖基转移酶活性，在一些物种中，这些蛋白已被证明是必不可少的。枯草芽孢杆菌基因组序列包含四个编码A类PBPs的基因，没有其他与其糖基转移酶结构域相似的基因。构建了一株缺乏所有四个A类PBPs的菌株，并产生了一种与野生型仅有微小结构差异的肽聚糖壁。四重突变体的生长速度远低于只缺少三个A类PBP的菌株，并且细胞长度和细胞壁异常的频率明显增加。四重突变菌株的活力和产壁能力表明，一种新的酶可以完成合成多肽多糖所需的糖基转移酶活性。这种活性在体外被证明，并且对糖基转移酶抑制剂莫诺霉素敏感。相反，四重突变株在体内对莫诺霉素具有抗药性。将野生型菌株暴露于莫诺霉素后，产生了与四重突变体相似的表型。
Penicillin-binding proteins (PBPs) catalyze the final, essential reactions of peptidoglycan synthesis. Three classes of PBPs catalyze either trans-, endo-, or carboxypeptidase activities on the peptidoglycan peptide side chains. Only the class A high-molecular-weight PBPs have clearly demonstrated glycosyltransferase activities that polymerize the glycan strands, and in some species these proteins have been shown to be essential. The Bacillus subtilis genome sequence contains four genes encoding class A PBPs and no other genes with similarity to their glycosyltransferase domain. A strain lacking all four class A PBPs has been constructed and produces a peptidoglycan wall with only small structural differences from that of the wild type. The growth rate of the quadruple mutant is much lower than those of strains lacking only three of the class A PBPs, and increases in cell length and frequencies of wall abnormalities were noticeable. The viability and wall production of the quadruple-mutant strain indicate that a novel enzyme can perform the glycosyltransferase activity required for peptidoglycan synthesis. This activity was demonstrated in vitro and shown to be sensitive to the glycosyltransferase inhibitor moenomycin. In contrast, the quadruple-mutant strain was resistant to moenomycin in vivo. Exposure of the wild-type strain to moenomycin resulted in production of a phenotype similar to that of the quadruple mutant.