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Androgen-metabolizing enzymes: A structural perspective.

Mahder Seifu Manenda1, Charles Jérémie Hamel1, Loreleï Masselot-Joubert1

  • 1Département de Biochimie, de Microbiologie et de Bio-informatique, PROTEO, Université Laval, Québec City, QC G1V 0A6, Canada; Institut de Biologie Intégrative et des Systèmes (IBIS), Université Laval, Pavillon Charles-Eugène-Marchand, Québec City, QC G1V 0A6, Canada.

The Journal of Steroid Biochemistry and Molecular Biology
|March 1, 2016
PubMed
Summary

Androgen-metabolizing enzymes, like P450s and Aldo-Keto Reductases (AKRs), transform cholesterol into vital signaling molecules. Understanding their structure aids in designing drugs for diseases such as cancer.

Keywords:
AKRsAndrogenAromataseInhibitorsP450sPDBStructure

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Area of Science:

  • Biochemistry
  • Enzymology
  • Molecular Biology

Background:

  • Cholesterol is converted into potent vertebrate signaling molecules by androgen-metabolizing enzymes.
  • This biotransformation involves complex reactions catalyzed by Cytochrome P450 enzymes and Aldo-Keto Reductases (AKRs).

Purpose of the Study:

  • To review the structures of androgen-metabolizing enzymes, focusing on active site interactions and catalytic mechanisms.
  • To highlight the application of structural knowledge in drug design for diseases linked to these enzymes, especially cancer.

Main Methods:

  • Structural analysis of P450 enzymes and AKRs.
  • Review of proposed catalytic mechanisms for androgen metabolism.
  • Examination of structure-based drug design strategies.

Main Results:

  • Detailed insights into the active sites of P450s and AKRs involved in androgen metabolism.
  • Elucidation of reaction mechanisms, including thermodynamically challenging steps.
  • Identification of key structural features relevant for therapeutic targeting.

Conclusions:

  • Structural understanding of androgen-metabolizing enzymes is crucial for elucidating their function.
  • This knowledge facilitates the development of targeted therapeutics for androgen-related diseases, including various cancers.