Human carboxylesterases: an update on CES1, CES2 and CES3.
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.
Sanghani
Sonal P
SP
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA. wbosron@iupui.edu
Sanghani
Paresh C
PC
Schiel
Marissa A
MA
Bosron
William F
WF
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D043182:Carboxylesterase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
C517204:CES2 protein, human; D043182:Carboxylesterase