期刊
CURRENT OPINION IN STRUCTURAL BIOLOGY
卷 74, 期 -, 页码 -出版社
CURRENT BIOLOGY LTD
DOI: 10.1016/j.sbi.2022.102369
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资金
- NIH [R21 AI154191, R01 GM135343]
- Welch Foundation [I-1957]
- Damon Runyon Cancer Research Foundation [DRR-53S-19]
- Rita C. and William P. Clements Jr. Scholar in Biomedical Research at UT Southwestern Medical Center
Cholesterol biosynthesis involves multiple enzymes, and understanding their structures and catalytic mechanisms can provide insights for drug development targeting related diseases.
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 3 beta-hydroxysteroid Delta(8)-Delta(7) 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.
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