Anantharaman Vivek, Aravind L
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Genome Biol. 2003;4(2):R11. doi: 10.1186/gb-2003-4-2-r11. Epub 2003 Feb 3.
Peptidoglycan is hydrolyzed by a diverse set of enzymes during bacterial growth, development and cell division. The N1pC/P60 proteins define a family of cell-wall peptidases that are widely represented in various bacterial lineages. Currently characterized members are known to hydrolyze D-gamma-glutamyl-meso-diaminopimelate or N-acetylmuramate-L-alanine linkages.
Detailed analysis of the N1pC/P60 peptidases showed that these proteins define a large superfamily encompassing several diverse groups of proteins. In addition to the well characterized P60-like proteins, this superfamily includes the AcmB/LytN and YaeF/YiiX families of bacterial proteins, the amidase domain of bacterial and kinetoplastid glutathionylspermidine synthases (GSPSs), and several proteins from eukaryotes, phages, poxviruses, positive-strand RNA viruses, and certain archaea. The eukaryotic members include lecithin retinol acyltransferase (LRAT), nematode developmental regulator Egl-26, and candidate tumor suppressor H-rev107. These eukaryotic proteins, along with the bacterial YaeF/poxviral G6R family, show a circular permutation of the catalytic domain. We identified three conserved residues, namely a cysteine, a histidine and a polar residue, that are involved in the catalytic activities of this superfamily. Evolutionary analysis of this superfamily shows that it comprises four major families, with diverse domain architectures in each of them.
Several related, but distinct, catalytic activities, such as murein degradation, acyl transfer and amide hydrolysis, have emerged in the N1pC/P60 superfamily. The three conserved catalytic residues of this superfamily are shown to be equivalent to the catalytic triad of the papain-like thiol peptidases. The predicted structural features indicate that the N1pC/P60 enzymes contain a fold similar to the papain-like peptidases, transglutaminases and arylamine acetyltransferases.
在细菌生长、发育和细胞分裂过程中，肽聚糖会被多种酶水解。N1pC/P60蛋白定义了一类细胞壁肽酶家族，广泛存在于各种细菌谱系中。目前已鉴定的成员已知可水解D-γ-谷氨酰-内消旋二氨基庚二酸或N-乙酰胞壁酸-L-丙氨酸连接键。
对N1pC/P60肽酶的详细分析表明，这些蛋白定义了一个大型超家族，包含几个不同的蛋白质组。除了特征明确的P60样蛋白外，这个超家族还包括细菌蛋白的AcmB/LytN和YaeF/YiiX家族、细菌和动质体谷胱甘肽亚精胺合酶（GSPS）的酰胺酶结构域，以及来自真核生物、噬菌体、痘病毒、正链RNA病毒和某些古菌的几种蛋白质。真核生物成员包括卵磷脂视黄醇酰基转移酶（LRAT）、线虫发育调节因子Egl-26和候选肿瘤抑制因子H-rev107。这些真核生物蛋白与细菌YaeF/痘病毒G6R家族一起，显示出催化结构域的环形排列。我们鉴定出三个保守残基，即一个半胱氨酸、一个组氨酸和一个极性残基，它们参与了这个超家族的催化活性。对这个超家族的进化分析表明，它由四个主要家族组成，每个家族都有不同的结构域结构。
在N1pC/P60超家族中出现了几种相关但不同的催化活性，如胞壁质降解、酰基转移和酰胺水解。这个超家族的三个保守催化残基被证明等同于木瓜蛋白酶样巯基肽酶的催化三联体。预测的结构特征表明，N1pC/P60酶含有与木瓜蛋白酶样肽酶、转谷氨酰胺酶和芳胺乙酰转移酶相似的折叠结构。
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