A nano switch mechanism for the redox-responsive sulfotransferase

Chih Heng Lin, En Shyh Lin, Tian Mu Su, Kuo Sheng Hung, Yuh Shyong Yang

研究成果: 雜誌貢獻文章

1 引文 (Scopus)

摘要

Cellular redox signaling is important in diverse physiological and pathological processes. The activity of rat phenol sulfotransferase (rSULT1A1), which is important for the metabolism of hormone and drug, is subjected to redox regulation. Two cysteines, Cys232 and Cys66, nanometer away from each other and from the enzyme active site were proposed to form disulfide bond to regulate the activity of rSULT1A1. A nano switch, composed of a flexible loop from amino acid residues 59-70, explained how this long distance interaction between two cysteines can be achieved. The enzyme properties were investigated through site-directed muatagnesis, circular dichroism, enzyme kinetics and homologous modeling of the rSULT1A1 structures. We proposed that the formation of disulfide bond between Cys232 and Cys66 induced conformational changes of sulfotransferase, then in turn affected its nucleotide binding and enzyme activity. This discovery was extended to understand the possible redox regulation of other sulfotransferases from different organisms. The redox switch can be created in other redox-insensitive sulfotransferases, such as human phenol sulfotransferase (hSULT1A1) and human alcohol sulfotransferase (hSULT2A1), to produce mutant enzymes with redox regulation capacity. This study strongly suggested that redox regulation of drug and hormone metabolism can be significantly varied even though the sequence and structure of SULT1A1 of human and rat have a high degree of homology.

原文英語
頁(從 - 到)224-231
頁數8
期刊Biochemical Pharmacology
84
發行號2
DOIs
出版狀態已發佈 - 七月 15 2012

指紋

Sulfotransferases
Oxidation-Reduction
Switches
Arylsulfotransferase
Enzymes
Metabolism
Disulfides
Cysteine
Rats
Hormones
Physiological Phenomena
Enzyme kinetics
Drug and Narcotic Control
Enzyme activity
Pathologic Processes
Circular Dichroism
Pharmaceutical Preparations
Catalytic Domain
Nucleotides
Amino Acids

ASJC Scopus subject areas

  • Pharmacology
  • Biochemistry

引用此文

A nano switch mechanism for the redox-responsive sulfotransferase. / Lin, Chih Heng; Lin, En Shyh; Su, Tian Mu; Hung, Kuo Sheng; Yang, Yuh Shyong.

於: Biochemical Pharmacology, 卷 84, 編號 2, 15.07.2012, p. 224-231.

研究成果: 雜誌貢獻文章

Lin, Chih Heng ; Lin, En Shyh ; Su, Tian Mu ; Hung, Kuo Sheng ; Yang, Yuh Shyong. / A nano switch mechanism for the redox-responsive sulfotransferase. 於: Biochemical Pharmacology. 2012 ; 卷 84, 編號 2. 頁 224-231.
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