Structural enzymology of cholesterol biosynthesis and storage

Tao Long, Erik W. Debler, Xiaochun Li

Research output: Contribution to journalReview articlepeer-review


Cholesterol biosynthesis occurs in the endoplasmic reticulum (ER). Its lego-like construction from water-soluble small metabolites via intermediates of increasing complexity to water-insoluble cholesterol requires numerous distinct enzymes. Dysfunction of the involved enzymes can cause several human inborn defects and diseases. Here, we review recent structures of three key cholesterol biosynthetic enzymes: Squalene epoxidase (SQLE), NAD(P)-dependent steroid dehydrogenase-like (NSDHL), and 3β-hydroxysteroid Δ87 isomerase termed EBP. Moreover, we discuss structures of acyl-CoA:cholesterol acyltransferase (ACAT) enzymes, which are responsible for forming cholesteryl esters from cholesterol to maintain cholesterol homeostasis in the ER. The structures of these enzymes reveal their catalytic mechanism and provide a molecular basis to develop drugs for treating diseases linked to their dysregulation.

Original languageEnglish (US)
Article number102369
JournalCurrent Opinion in Structural Biology
StatePublished - Jun 2022

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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