Sanghani Sonal P, Sanghani Paresh C, Schiel Marissa A, Bosron William F
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Protein Pept Lett. 2009;16(10):1207-14. doi: 10.2174/092986609789071324.
Carboxylesterases belong to Phase I group of drug metabolizing enzymes. They hydrolyze a variety of drug esters, amides, carbamates and similar structures. There are five 'carboxylesterase' genes listed in the Human Genome Organization database. In this review, we will focus on the CES1, CES2 and CES3 genes and their protein products that have been partially characterized. Several variants of these three CESs result from alternate splicing, single nucleotide polymorphisms and multiple copy variants. The three CESs, are largely localized to tissues that are major sites of drug metabolism like the mucosa of the gastrointestinal tract, lungs and liver but, they differ in tissue-specific expression. The amino acid alignment of the three CESs reveals important conserved catalytic and structural residues. There are interesting insertions and deletions that may affect enzymatic function as determined by homology modeling of CES3 using the CES1 three-dimensional structure. A comparison of the substrate specificity of CES1 versus CES2 reveals broad but distinct substrate preferences. There is little information on the substrate specificity of CES3 but it seems to have a lower catalytic efficiency than the other two CESs for selected substrates.
羧酸酯酶属于药物代谢酶的I相酶类。它们能水解多种药物酯、酰胺、氨基甲酸酯及类似结构。人类基因组组织数据库中列出了五个“羧酸酯酶”基因。在本综述中，我们将聚焦于已得到部分表征的CES1、CES2和CES3基因及其蛋白质产物。这三种羧酸酯酶的多个变体源于可变剪接、单核苷酸多态性和多拷贝变体。这三种羧酸酯酶主要定位于药物代谢的主要场所，如胃肠道黏膜、肺和肝脏等组织，但它们在组织特异性表达方面存在差异。这三种羧酸酯酶的氨基酸序列比对揭示了重要的保守催化和结构残基。通过使用CES1三维结构对CES3进行同源建模确定，存在一些可能影响酶功能的有趣插入和缺失。CES1与CES2底物特异性的比较揭示了广泛但不同的底物偏好。关于CES3底物特异性的信息很少，但对于选定的底物，它似乎比其他两种羧酸酯酶具有更低的催化效率。
