肺炎链球菌双模块A类青霉素结合蛋白的突变分析
Mutational analysis of the Streptococcus pneumoniae bimodular class A penicillin-binding proteins.
作者信息
Paik J, Kern I, Lurz R, Hakenbeck R
机构信息
Max-Planck Institut für Molekulare Genetik, D-14185 Berlin, Germany.
出版信息
J Bacteriol. 1999 Jun;181(12):3852-6. doi: 10.1128/JB.181.12.3852-3856.1999.
Abstract
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.
摘要
一类青霉素靶标酶，即A类高分子量青霉素结合蛋白（PBPs），是双模块酶。除了一个中央青霉素结合转肽酶结构域外，它们还含有一个N端假定糖基转移酶结构域。通过在糖基转移酶结构域内进行插入重复诱变，分离出肺炎链球菌三种A类PBPs（PBP1a、PBP1b和PBP2a）各自基因中的突变，证明它们的功能在实验室中对细胞生长并非必不可少。也可以分离出PBP1b PBP2a和PBP1a PBP1b双突变体，两者都表现出隔膜定位缺陷。获得PBP2a PBP1a双突变体的尝试失败了。所有pbp2a基因被破坏的突变体对莫能菌素表现出更高的敏感性，莫能菌素是一种已知能抑制PBP相关糖基转移酶活性的抗生素，表明PBP2a是肺炎链球菌中糖基转移酶抑制剂的主要靶标。
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