TY - JOUR
T1 - Structural enzymology of cholesterol biosynthesis and storage
AU - Long, Tao
AU - Debler, Erik W.
AU - Li, Xiaochun
N1 - Funding Information:
We apologize to our colleagues whose work could not be cited due to space limitations. This work was supported by NIH grant R21 AI154191 (E.W.D), R01 GM135343 and Welch Foundation ( I-1957 ) (to X.L.). X.L. is a Damon Runyon-Rachleff Innovator supported by the Damon Runyon Cancer Research Foundation ( DRR - 53S -19 ) and a Rita C. and William P. Clements Jr. Scholar in Biomedical Research at UT Southwestern Medical Center.
Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/6
Y1 - 2022/6
N2 - 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 Δ8-Δ7 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.
AB - 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 Δ8-Δ7 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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U2 - 10.1016/j.sbi.2022.102369
DO - 10.1016/j.sbi.2022.102369
M3 - Review article
C2 - 35398802
AN - SCOPUS:85127809802
SN - 0959-440X
VL - 74
JO - Current Opinion in Structural Biology
JF - Current Opinion in Structural Biology
M1 - 102369
ER -