Mutational analysis of the Streptococcus pneumoniae bimodular class a penicillin-binding proteins
Mutational analysis of the Streptococcus pneumoniae bimodular class a penicillin-binding proteins
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DOI：
10.1128/jb.181.12.3852-3856.1999
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发表时间：
1999-06-01
影响因子：
3.2
通讯作者：
Hakenbeck, R
中科院分区：
文献类型：
--
作者：
Paik, J;Kern, I;Hakenbeck, R
一类青霉素靶酶，A类高分子量青霉素结合蛋白（PBPs），是双模酶。除了中央青霉素结合转肽酶结构域外，它们还含有n端假定的糖基转移酶结构域。通过糖基转移酶结构域内的插入复制诱变分离出三种肺炎链球菌a类PBPs （PBP1a、PBP1b和PBP2a）的基因突变，证明它们的功能在实验室中对细胞生长不是必需的。PBP1b、PBP2a、PBP1a、PBP1b双突变体也可以分离得到，均表现出鼻中隔定位缺陷，试图获得PBP2a、PBP1a双突变体失败。所有pbp2a基因被破坏的突变体对莫诺霉素（一种已知能抑制pbp相关糖基转移酶活性的抗生素）都表现出更高的敏感性，这表明pbp2a是肺炎链球菌糖基转移酶抑制剂的主要靶点。
One group of penicillin target enzymes, the class A high-molecular-weight penicillin-binding proteins (PBPs), are bimodular enzymes. In addition to a central penicillin-binding-transpeptidase domain, they contain an N-terminal putative glycosyltransferase domain, Mutations in the genes for each of the three Streptococcus pneumoniae class A PBPs, PBP1a, PBP1b, and PBP2a, were isolated by insertion duplication mutagenesis within the glycosyltransferase domain, documenting that their function is not essential for cellular growth in the laboratory. PBP1b PBP2a and PBP1a PBP1b double mutants could also be isolated, and both showed defects in positioning of the septum, Attempts to obtain a PBP2a PBP1a double mutant failed. All mutants with a disrupted pbp2a gene showed higher sensitivity to moenomycin, an antibiotic known to inhibit PBP-associated glycosyltransferase activity, indicating that PBP2a is the primary target for glycosyltransferase inhibitors in S, pneumoniae.