IDENTIFICATION OF VANCOMYCIN RESISTANCE PROTEIN VANA AS A D-ALANINE - D-ALANINE LIGASE OF ALTERED SUBSTRATE-SPECIFICITY
IDENTIFICATION OF VANCOMYCIN RESISTANCE PROTEIN VANA AS A D-ALANINE - D-ALANINE LIGASE OF ALTERED SUBSTRATE-SPECIFICITY
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DOI：
10.1021/bi00222a002
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发表时间：
1991-02-26
期刊：
影响因子：
2.9
通讯作者：
WALSH, CT
中科院分区：
文献类型：
--
作者：
BUGG, TDH;DUTKAMALEN, S;WALSH, CT
屎肠球菌BM4147的高水平糖肽抗性是由一个38 kDa的Vana蛋白介导的，其氨基酸序列与革兰氏阴性D-丙氨酸：D-丙氨酸(D-Ala-D-Ala)连接酶[duka-Malen，S.，Molinas，C.，Arthur，M.和Courvalin，P.(1990)Mol.]有关。吉内特将军。224、364-372]。我们报道了VANA的纯化，并证明了它具有D-ALA-D-ALA连接酶活性，但与革兰氏阴性D-ALA-D-ALA连接酶相比，它具有显著的底物特异性。Vana优先将D-Ala与D-Met或D-Phe缩合，增加了其细胞作用是合成修饰的细胞壁成分的可能性，该成分随后不被万古霉素识别。
High-level glycopeptide resistance in Enterococcus faecium BM4147 is mediated by a 38-kDa protein VanA, whose amino acid sequence is related to Gram-negative D-alanine:D-alanine (D-Ala-D-Ala) ligases [Dutka-Malen, S., Molinas, C., Arthur, M., & Courvalin, P. (1990) Mol. Gen. Genet. 224, 364-372]. We report purification of VanA and demonstrate that it has D-Ala-D-Ala ligase activity but has substantially modified substrate specificity, compared with Gram-negative D-Ala-D-Ala ligases. VanA preferentially condenses D-Ala with D-Met or D-Phe, raising the possibility that its cellular role is to synthesize a modified cell-wall component, which is subsequently not recognized by vancomycin.