Androgen-metabolizing enzymes: A structural perspective

J Steroid Biochem Mol Biol. 2016 Jul:161:54-72. doi: 10.1016/j.jsbmb.2016.02.021. Epub 2016 Feb 24.

Abstract

Androgen-metabolizing enzymes convert cholesterol, a relatively inert molecule, into some of the most potent chemical messengers in vertebrates. This conversion involves thermodynamically challenging reactions catalyzed by P450 enzymes and redox reactions catalyzed by Aldo-Keto Reductases (AKRs). This review covers the structures of these enzymes with a focus on active site interactions and proposed mechanisms. Due to their role in a number of diseases, particularly in cancer, androgen-metabolizing enzymes have been targets of drug design. Hence we will also highlight how existing knowledge of structure is being used to this end.

Keywords: AKRs; Androgen; Aromatase; Inhibitors; P450s; PDB; Structure.

Publication types

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

MeSH terms

  • 17-Hydroxysteroid Dehydrogenases / chemistry
  • 17-Hydroxysteroid Dehydrogenases / metabolism*
  • 3-Hydroxysteroid Dehydrogenases / chemistry
  • 3-Hydroxysteroid Dehydrogenases / metabolism*
  • Androgens / chemistry
  • Androgens / metabolism*
  • Animals
  • Cytochrome P-450 Enzyme System / chemistry
  • Cytochrome P-450 Enzyme System / metabolism*
  • Humans
  • Metabolic Networks and Pathways
  • Models, Molecular
  • Oxidoreductases / chemistry
  • Oxidoreductases / metabolism*

Substances

  • Androgens
  • Cytochrome P-450 Enzyme System
  • Oxidoreductases
  • 17-Hydroxysteroid Dehydrogenases
  • 3-Hydroxysteroid Dehydrogenases
  • 3-oxo-5 beta-steroid delta 4-dehydrogenase