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Acyl-Coenzyme A:cholesterol Acyltransferase 1: Significance of Single Nucleotide Polymorphism at Residue 526 and Role of Proline 347 near the Fifth Transmembrane Domain.

FEBS J.. 2014-02; 
Huang LH, Nishi K, Li S, Ho T, Dong R, Chang CC, Chang TY. Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, 03755.
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摘要

Acyl-Coenzyme A:cholesterol Acyltransferases (ACATs), members of the membrane bound O-acyltransferase (MBOAT) family, catalyze the conversion of cholesterol to cholesteryl esters. Mammals contain two isoenzymes ACAT1 and ACAT2. Both enzymes are drug targets for treating human diseases. ACAT1 is present ubiquitously in various cell types. It contains 9 transmembrane domains (TMDs) with the active site H460 locating within TMD #7, and another active site N421 locating within the 4th large cytoplasmic loop. In human ACAT1, a single nucleotide polymorphism (SNP) exists for residue 526: the codon is either CAG for glutamine (Q), or CGG for arginine (R). Q/R 526 is present within the C-terminal loop. Its biochemical ... More

关键词

Alzheimer's disease; Atherosclerosis; Cholesterol metabolism; Single nucleotide polymorphism; Site-specific mutagenesis