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Molecular cloning and biochemical characterization of Candida albicans acyl-CoA:sterol acyltransferase, a potential target of antifungal agents

Authors
 Young-Ki Paik  ;  Ki-Young Kim  ;  Dong-Min Han  ;  Hongyuan Yang  ;  Jung-Ho Kim  ;  Jong-Chul Park  ;  Yu-Kyong Shin 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.319(3) : 911-919, 2004 
Journal Title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN
 0006-291X 
Issue Date
2004
Keywords
Acyl-coenzyme A:sterol acyltransferase ; Ergosterol ; Sterol ester ; Candida albicans ; Antifungal agent ; HWY-289
Abstract
To determine whether Candida albicans acyl CoA:sterol acyltransferase (ASAT) can be a potential target enzyme for the protoberberine derivative (HWY-289), we have isolated a gene encoding Ca-ASAT and examined inhibitory effects of HWY-289 on the overexpressed Ca-ASAT. HWY-289 specifically inhibits Ca-ASAT in a non-competitive manner in vitro (IC50 [9.2 μM], Ki [5.15 μM]). The cloned CaARE2 gene (1830 nucleotides [nt]) encodes active Ca-ASAT protein that exhibits a calculated molecular mass of 71.3 kDa. The amino acid sequence of CaAre2p is 33.4% and 35.1% identical to those of Saccharomyces cerevisiae ScAre1p and ScAre2p homologues, respectively. Recombinant and endogenous Ca-ASAT displayed identical patterns of inhibition upon exposure to HWY-289 and a preference for cholesterol and oleoyl-CoA as substrates. Northern blot analysis showed that CaARE2 was activated by HWY-289, but not by CI-976 (a human acyl-coenzyme A:cholesterol acyltransferase inhibitor), in a dose-dependent manner (up to 5 mg/L), suggesting different selectivities of action between HWY-289 and CI-976 on Ca-ASAT activity.
Full Text
http://www.sciencedirect.com/science/article/pii/S0006291X04010435
DOI
10.1016/j.bbrc.2004.05.076
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Medical Engineering (의학공학교실) > 1. Journal Papers
Yonsei Authors
Park, Jong Chul(박종철) ORCID logo https://orcid.org/0000-0003-0083-5991
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/111550
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