Determination and use of a transition state for the enzyme estrone sulfatase (ES) from a proposed reaction mechanism

Bioorg Med Chem Lett. 2001 Dec 3;11(23):3001-5. doi: 10.1016/s0960-894x(01)00607-2.

Abstract

Using the postulated mechanism for the enzyme estrone sulfatase (ES), we have determined a possible transition state for the reaction catalysed by ES as a representation of the active site. Using the derived structure, we have undertaken the molecular modelling of several steroidal and non-steroidal inhibitors in an attempt to rationalise the inhibitory activity of a number of potent inhibitors.

MeSH terms

  • Catalytic Domain
  • Coumarins / pharmacology
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Estrone / analogs & derivatives*
  • Estrone / chemistry
  • Estrone / pharmacology
  • Inhibitory Concentration 50
  • Models, Molecular*
  • Protein Conformation
  • Structure-Activity Relationship
  • Sulfatases / antagonists & inhibitors
  • Sulfatases / chemistry*
  • Sulfatases / metabolism*
  • Sulfonamides / pharmacology
  • Sulfonic Acids

Substances

  • Coumarins
  • Enzyme Inhibitors
  • Sulfonamides
  • Sulfonic Acids
  • estrone-3-O-sulfamate
  • Estrone
  • irosustat
  • Sulfatases
  • estrone sulfatase