A Novel Acyl-AcpM-Binding Protein Confers Intrinsic Sensitivity to Fatty Acid Synthase Type II Inhibitors in Mycobacterium smegmatis.
A Novel Acyl-AcpM-Binding Protein Confers Intrinsic Sensitivity to Fatty Acid Synthase Type II Inhibitors in Mycobacterium smegmatis.
复制标题
DOI：
10.3389/fmicb.2022.846722
复制
发表时间：
2022
影响因子：
5.2
通讯作者：
Zhang, Junjie
中科院分区：
文献类型：
--
作者：
Li, Mengmiao;Huang, Qian;Zhang, Weidi;Cao, Yinghua;Wang, Zhanxin;Zhao, Zhenwen;Zhang, Xiaotian;Zhang, Junjie
The fatty acid synthase type II (FAS-II) multienzyme system is the main target of drugs to inhibit mycolic acid synthesis in mycobacterium. Meromycolate extension acyl carrier protein (AcpM) serves as the carrier of fatty acyl chain shuttling among the individual FAS-II components during the progression of fatty acid elongation. In this paper, MSMEG_5634 in Mycobacterium smegmatis was determined to be a helix-grip structure protein with a deep hydrophobic pocket, preferring to form a complex with acyl-AcpM containing a fatty acyl chain at the C36-52 length, which is the medium product of FAS-II. MSMEG_5634 interacted with FAS-II components and presented relative accumulation at the cellular pole. By forming the MSMEG_5634/acyl-AcpM complex, which is free from FAS-II, MSMEG_5634 could transport acyl-AcpM away from FAS-II. Deletion of the MSMEG_5634 gene in M. smegmatis resulted in a mutant with decreased sensitivity to isoniazid and triclosan, two inhibitors of the FAS-II system. The isoniazid and triclosan sensitivity of this mutant could be restored by the ectopic expression of MSMEG_5634 or Rv0910, the MSMEG_5634 homologous protein in Mycobacterium tuberculosis H37Rv. These results suggest that MSMEG_5634 and its homologous proteins, forming a novel acyl-AcpM-binding protein family in mycobacterium, confer intrinsic sensitivity to FAS-II inhibitors.
登录
查看更多内容
DOI：
10.1073/pnas.0709223105
发表时间：
2008-04-08
影响因子：
11.1
作者：
Ames, Brian Douglas;Korman, Tyler Paz;Tsai, Shiou-Chuan
通讯作者：
Tsai, Shiou-Chuan
影响因子：
4.8
作者：
Kremer, L;Nampoothiri, KM;Besra, GS
通讯作者：
Besra, GS
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
2.8
作者：
Parish, T;Stoker, NG
通讯作者：
Stoker, NG
影响因子：
3.7
作者：
Pawelczyk, Jakub;Kremer, Laurent
通讯作者：
Kremer, Laurent