Inhibiting bacterial fatty acid synthesis

被引:204
作者
Zhang, Yong-Mei
White, Stephen W.
Rock, Charles O.
机构
[1] St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA
[2] St Jude Childrens Res Hosp, Dept Struct Biol, Memphis, TN 38105 USA
关键词
D O I
10.1074/jbc.R600004200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The type II fatty acid synthase consists of a series of individual enzymes, each encoded by a separate gene, that catalyze discrete steps in chain elongation. The formation of fatty acids is vital to bacteria, and each of the essential enzymes and their acyl group carriers represent a potential target for the development of novel antibacterial therapeutics. High resolution x-ray and/or NMR structures of representative members of every enzyme in the type II pathway are now available, and these structures are a valuable resource to guide antibacterial drug discovery. The role of each enzyme in regulating pathway activity and the diversity in the components of the pathway in the major human pathogens are important considerations in deciding the most suitable targets for future drug development.
引用
收藏
页码:17541 / 17544
页数:4
相关论文
共 99 条
[1]   A mechanism of drug action revealed by structural studies of enoyl reductase [J].
Baldock, C ;
Rafferty, JB ;
Sedelnikova, SE ;
Baker, PJ ;
Stuitje, AR ;
Slabas, AR ;
Hawkes, TR ;
Rice, DW .
SCIENCE, 1996, 274 (5295) :2107-2110
[2]   INHA, A GENE ENCODING A TARGET FOR ISONIAZID AND ETHIONAMIDE IN MYCOBACTERIUM-TUBERCULOSIS [J].
BANERJEE, A ;
DUBNAU, E ;
QUEMARD, A ;
BALASUBRAMANIAN, V ;
UM, KS ;
WILSON, T ;
COLLINS, D ;
DELISLE, G ;
JACOBS, WR .
SCIENCE, 1994, 263 (5144) :227-230
[3]   Characterization of a new pantothenate kinase isoform from Helicobacter pylori. [J].
Brand, LA ;
Strauss, E .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (21) :20185-20188
[4]   Bacterial fatty acid biosynthesis: Targets for antibacterial drug discovery [J].
Campbell, JW ;
Cronan, JE .
ANNUAL REVIEW OF MICROBIOLOGY, 2001, 55 :305-332
[5]   Long-term effects of a fatty acid synthase inhibitor on obese mice: food intake, hypothalamic neuropeptides, and UCP3 [J].
Cha, SH ;
Hu, ZY ;
Lane, MD .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2004, 317 (02) :301-308
[6]   Crystal structure of Streptococcus pneumoniae acyl carrier protein synthase:: an essential enzyme in bacterial fatty acid biosynthesis [J].
Chirgadze, NY ;
Briggs, SL ;
McAllister, KA ;
Fischl, AS ;
Zhao, GS .
EMBO JOURNAL, 2000, 19 (20) :5281-5287
[7]   Structure elucidation of Sch 538415, a novel acyl carrier protein synthase inhibitor from a microorganism [J].
Chu, M ;
Mierzwa, R ;
Xu, L ;
Yang, SW ;
He, L ;
Patel, M ;
Stafford, J ;
Macinga, D ;
Black, T ;
Chan, TM ;
Gullo, V .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (21) :3827-3829
[8]   N1-(SUBSTITUTED) PANTOTHENAMIDES, ANTIMETABOLITES OF PANTOTHENIC ACID [J].
CLIFTON, G ;
BRYANT, SR ;
SKINNER, CG .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1970, 137 (02) :523-&
[9]   Multi-subunit acetyl-CoA carboxylases [J].
Cronan, JE ;
Waldrop, GL .
PROGRESS IN LIPID RESEARCH, 2002, 41 (05) :407-435
[10]   Bacterial membrane lipids: Where do we stand? [J].
Cronan, JE .
ANNUAL REVIEW OF MICROBIOLOGY, 2003, 57 :203-224