Rat NTE-related esterase is a membrane-associated protein, hydrolyzes phenyl valerate, and interacts with diisopropylfluorophosphate through a serine catalytic machinery.
The serine hydrolases constitute multi-families of proteins that include lipases, esterases, and proteases. These enzymes contain a signature motif GXSXG, in which the serine residue acts as the nucleophile and initiates catalysis. This report describes the characterization of a novel serine hydrolase from rat. This enzyme exhibits a moderate sequence identity with the neuropathy target esterase (NTE), thus is designated NTE-related esterase (NRE). Transfection with the NRE cDNA resulted in marked increases in the hydrolysis of phenyl valerate and reactivity with diisopropylfluorophosphate. Such increases, however, were markedly or completely abolished in mutants that had a substitution (Ala, Cys, Asp, or His) on the serine residue in the GXSXG motif, providing direct evidence that NRE is a serine hydrolase. By Northern blot analyses, three NRE transcripts were detected and they differed markedly in length (approximately 2.6, 4.2, and 5.0 kb). The 4.2-kb transcript was present in all organs analyzed except the testis, in which both 2.6- and 5.0-kb transcripts were detected. The testicular transcripts were completely depleted in rats treated with clofibrate, whereas the levels of NRE mRNA in the liver were markedly increased in rats treated with perfluorodecanoic acid. Both clofibrate and perfluorodecanoic acid are efficacious activators of the peroxisome proliferator activated receptor-alpha (PPAR-alpha). The differential effects on the levels of NRE mRNA suggest that these chemicals regulate the expression of NRE through mechanism(s) rather than the activation of PPAR-alpha.
Xie
Mingxing
M
Department of Biomedical Sciences, University of Rhode Island, Kingston, RI 02881, USA.
Yang
Dongfang
D
Matoney
Lynn
L
Yan
Bingfang
B
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006868:Hydrolysis; D007531:Isoflurophate / Q000378:metabolism*; D007668:Kidney / Q000737:chemistry / Q000196:embryology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009928:Organ Specificity; D051381:Rats / Q000235:genetics; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D013045:Species Specificity; D014018:Tissue Distribution; D014162:Transfection; D014631:Valerates / Q000378:metabolism*
D008565:Membrane Proteins; D011994:Recombinant Proteins; D014631:Valerates; D007531:Isoflurophate; C049867:phenyl valerate; D012694:Serine; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase