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  • 03월 10일 13시 이후 : 초록수정 불가능, 일정확인 및 검색만 가능

대한화학회 제105회 학술발표회 및 총회 Discovery of novel and potent inhibitors of beta-ketoacyl-acyl carrier protein synthase by NMR spectroscopy and in silico screening

등록일
2010년 3월 9일 15시 06분 48초
접수번호
1461
발표코드
금13C1심 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
발표시간
금 09시 : 30분
발표형식
심포지엄
발표분야
생명화학 - 단백질 과학의 생화학적 접근
저자 및
공동저자
김양미
건국대학교 생명공학과, Korea
The rise of multidrug-resistant of most bacteria requires the development of new antibiotics. Beta-Ketoacyl acyl carrier protein synthase (KAS) III is a particularly attractive target in the type II fatty acid synthetic pathway, since it is central to the initiation of fatty acid synthesis. In the present study, we used comparative homology modeling and receptor-oriented pharmacophore-based in silico screening to find the candidates of inhibitors for KAS III from S. aureus, E. coli, and E. faecalis. Binding study of selected compounds was performed by Saturation Transfer Difference (STD) NMR spectroscopy, fluorescence experiments and antimicrobial effect was evaluated against various antibiotic-resistant bacteria. From this study, we found several potent inhibitors of ecKAS III and efKAS III which showed an antimicrobial effect against E. coli and E. faecalis and we confirmed the importance of KAS III as targets for antimicrobial agents. Acyl carrier protein (ACP) is a small (~9 kDa) acidic protein whose function is essential for numerous biosynthetic pathways that depend upon acyl group transfer. Here, we investigated dynamic properties of ACP through observation of spin relaxation parameters. Backbone dynamics of ACP shows that extensive mobility in α1α2 loop and the N-terminal residues exhibit a conformational exchange process. HSQC spectra of holo-ACP showed two sets of resonances, suggesting that two conformers are in dynamic equilibrium. However, acyl-ACP has only one set of resonances. NMR data of acyl-ACP revealed that changes in the length of the covalently attached fatty acid affect the local conformation and the dynamics of ACP. Flexibility of ACP shown in this study is essential for its ability to interact with functionally different enzyme partners including KAS III in fatty acid synthetic pathway of bacteria.

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