Clugston S L, Honek J F
Department of Chemistry, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
J Mol Evol. 2000 May;50(5):491-5. doi: 10.1007/s002390010052.
The ubiquitous glyoxalase system, which is composed of two enzymes, removes cellular cytotoxic methylglyoxal (MG). In an effort to identify critical residues conserved in the evolution of the first enzyme in this system, glyoxalase I (GlxI), as well as the structural implications of sequence alterations in this enzyme, a search of the National Center for Biotechnology Information (NCBI) database of unfinished genomes was undertaken. Eleven putative GlxI sequences from pathogenic organisms were identified and analyses of these sequences in relation to the known and previously identified GlxI enzymes were performed. Several of these sequences show a very high similarity to the Escherichia coli GlxI sequence, most notably the 79% identity of the sequence identified from Yersinia pestis, the causative agent of bubonic plague. In addition to the conservation of residues critical to binding the catalytic metal in all of the proposed GlxI enzymes, four regions in the Homo sapiens GlxI enzyme are absent in all of the bacterial GlxI sequences, with the exception of Pseudomonas putida. Removal of these regions may alter the active-site conformation of the bacterial enzymes in relation to that of the H. sapiens. These differences may be targeted for the development of inhibitors selective to the bacterial enzymes.
普遍存在的乙二醛酶系统由两种酶组成，可清除细胞毒性甲基乙二醛（MG）。为了确定该系统中第一种酶即乙二醛酶I（GlxI）在进化过程中保守的关键残基，以及该酶序列改变的结构影响，我们对美国国立生物技术信息中心（NCBI）的未完成基因组数据库进行了搜索。从致病生物中鉴定出11个推定的GlxI序列，并对这些序列与已知的和先前鉴定的GlxI酶进行了分析。其中几个序列与大肠杆菌GlxI序列具有很高的相似性，最显著的是从腺鼠疫病原体鼠疫耶尔森菌中鉴定出的序列具有79%的同一性。除了在所有提议的GlxI酶中对结合催化金属至关重要的残基保守外，人源GlxI酶中的四个区域在所有细菌GlxI序列中均不存在，但恶臭假单胞菌除外。去除这些区域可能会改变细菌酶相对于人源酶的活性位点构象。这些差异可能成为开发对细菌酶具有选择性的抑制剂的靶点。
