From sequence and structure of sulfotransferases and dihydropyrimidinases to an understanding of their mechanisms of action and function

Expert Opin Drug Metab Toxicol. 2010 May;6(5):591-601. doi: 10.1517/17425251003601987.

Abstract

Importance of the field: Most enzymes that catalyze physiologically important reactions are known to be highly efficient and specific to their particular substrates. On the contrary, the enzymes of detoxification are known to catalyze unlimited number of substrates containing similar function groups that may have significant structural variation. This review explores nature's strategy to design enzymes with special properties.

Areas covered in this review: We review articles from 1981 to 2009, with special focus on the relationships of sequence, structure and function of cytosolic sulfotransferases and dihydropyrimidinase (DHP).

What the reader will gain: Specific amino acids responsible for substrate inhibition, substrate binding orientations, substrate specificity, quaternary structures and inactivation of sulfotransferases and DHP related enzymes are elucidated. Susceptibility to some diseases possibly resulted from the mutation of a single amino acid that causes dysfunction of these enzymes. Terminal deletion of amino acid that may affect surface interaction, subunit dissociation, stability alteration and then cause the syndrome of DHP deficiency is discussed.

Take home message: Based on the multiple sequence/structure analysis and with sufficient information from other members of the same enzyme families, the origin and mechanism of specific enzyme actions and proteins assembly can be clarified and predicted.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amidohydrolases / chemistry
  • Amidohydrolases / metabolism*
  • Amino Acid Sequence
  • Cytosol / enzymology
  • Genetic Predisposition to Disease
  • Humans
  • Mutation
  • Protein Structure, Quaternary
  • Protein Structure, Secondary
  • Substrate Specificity
  • Sulfotransferases / chemistry
  • Sulfotransferases / metabolism*

Substances

  • Sulfotransferases
  • Amidohydrolases
  • dihydropyrimidinase