Bujnicki J M, Rychlewski L
Bioinformatics Laboratory, International Institute of Molecular and Cell Biology, Warsaw, Poland.
Acta Microbiol Pol. 2001;50(1):7-17.
Methylation of G1405 within bacterial 16S ribosomal RNA results in high-level resistance to specific combinations of aminoglycoside antibiotics. Only a few closely related methyltransferases (MTases), which carry out the respective modification (here dubbed "Agr", for aminoglycoside resistance), are known. It is not clear, whether they are related to "typical" S-adenosylmethionine (AdoMet)-dependent MTases or not. Demydchuk et al., 1998 proposed that the cofactor-binding region is localized at the C-terminus of Agr MTases, which implies an interesting case of sequence permutation. Since the Agr MTases lack significant sequence similarity to other proteins, we tested that hypothesis using more sensitive sequence/structure threading approach. Structure prediction confirmed the presence of a putative AdoMet-binding site in these proteins, albeit at a distinct location, resembling that of "typical", non-permuted MTases. Additionally, a small alpha-helical domain dissimilar to other proteins in the database was identified in the N-terminal region of Agr MTases. Comparison of a three-dimensional model of the Agr family member with a recently solved structure of reovirus mRNA capping MTase suggests that the mechanism of guanine-N7 methylation in rRNA and mRNA may be different.
细菌16S核糖体RNA中G1405位点的甲基化导致对特定组合的氨基糖苷类抗生素产生高水平耐药性。目前已知仅有少数几种密切相关的甲基转移酶（MTases）能进行相应修饰（此处称为“Agr”，即氨基糖苷类耐药相关）。尚不清楚它们是否与“典型的”依赖S-腺苷甲硫氨酸（AdoMet）的甲基转移酶相关。Demydchuk等人在1998年提出，辅因子结合区域位于Agr甲基转移酶的C末端，这意味着存在一种有趣的序列重排情况。由于Agr甲基转移酶与其他蛋白质缺乏显著的序列相似性，我们使用更敏感的序列/结构穿线法来检验这一假设。结构预测证实这些蛋白质中存在一个假定的AdoMet结合位点，尽管位置不同，但类似于“典型的”、未重排的甲基转移酶。此外，在Agr甲基转移酶的N末端区域鉴定出一个与数据库中其他蛋白质不同的小α螺旋结构域。将Agr家族成员的三维模型与最近解析的呼肠孤病毒mRNA加帽甲基转移酶结构进行比较，结果表明rRNA和mRNA中鸟嘌呤-N7甲基化的机制可能不同。
