期刊
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY D-GENOMICS & PROTEOMICS
卷 4, 期 3, 页码 209-217出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cbd.2009.03.002
关键词
Mammals; Amino acid sequence; Genomics; Carboxylesterase; CES6; Drug detoxification
资金
- NIH [P01 HL028972, P51 RR013986]
- Research Facilities Improvement Program [1 C06 RR13556, 1 C06 RR15456, 1 C06 RR017515]
Mammalian carboxylesterases (CES) exhibit broad substrate specificities, catalyse hydrolytic and transesterification reactions with a wide range of drugs and xenobiotics and are widely distributed in the body. Four CES classes have been previously described, namely CES1 (major liver form); CES2 (major intestinal form); CES3 (highest activity in the colon): and CES5, a secreted enzyme found in mammalian kidney and male reproductive fluids. In silica methods were used to predict the amino acid sequences, structures and gene locations for a new class of CES genes and proteins, designated as CES6. Mammalian CES6 amino acid sequence alignments and predicted secondary and tertiary structures enabled the identification of key CES sequences previously reported for human CES1, but with CES6 specific sequences and properties: high isoelectric points (pI values of 8.8-9.4 compared with 5.4-6.2 for human CES1, CES2, CES3 and CES5); being predicted for secretion into body fluids compared with human CES1, human CES2 and CES3, which are membrane bound; and having Asn or Glu residues at the predicted CES1 Z-site for which a Gly residue plays a major role in cholesterol binding. Mammalian CES6 genes are located in tandem with CES2 and CES3 genes, are transcribed on the positive DNA strand and contain 14 exons. Human and mouse CES6-like transcripts have been previously reported to be widely distributed in the body but are localized in specific regions of the brain, including the cerebellum. CES6 may play a role in the detoxification of drugs and xenobiotics in neural and other tissues of the body and in the cerebrospinal fluid. (C) 2009 Elsevier Inc. All rights reserved.
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