Sequence analysis and expression of the cDNA for the phenol-sulfating form of human liver phenol sulfotransferase.
A cDNA encoding the human liver phenol-sulfating form of phenol sulfotransferase (P-PST) has been isolated and characterized from a lambda Uni-Zap XR human liver cDNA library. P-PST is the major form of phenol sulfotransferase involved in drug and xenobiotic metabolism in human liver. P-PST is also responsible for the sulfation and activation of minoxidil to its therapeutically active sulfate ester. The full length cDNA, P-PST-1, is 1206 base pairs in length and encodes a 295-amino acid protein with a molecular mass of 34,097 Da. The translation sequence of P-PST-1 is 96% similar to the amino acid sequences of five peptides derived from the purified protein. In vitro transcription and translation of P-PST-1 generated a protein that comigrates with immunoreactive P-PST from human liver. Significant increases in sulfotransferase activity toward two P-PST-specific substrates, minoxidil and 4-nitrophenol, were detected in cytosol prepared from COS-7 cells transfected with P-PST-1 in the expression vector p-SV-SPORT-1. Northern blot analysis of human liver RNA detected a transcript of approximately 1300 nucleotides in length. Characterization of P-PST at the molecular level provides insight into the structure and heterogeneity of this major class of drug-metabolizing enzymes.
Wilborn
T W
TW
Department of Pharmacology, University of Alabama, Birmingham 35294.
Comer
K A
KA
Dooley
T P
TP
Reardon
I M
IM
Heinrikson
R L
RL
Falany
C N
CN
D000595:Amino Acid Sequence; D015239:Arylsulfotransferase / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D014158:Transcription, Genetic
D004247:DNA; D015239:Arylsulfotransferase