Premium
Crystal structure of Streptococcus pneumoniae acyl carrier protein synthase: an essential enzyme in bacterial fatty acid biosynthesis
Author(s) -
Chirgadze Nickolay Y.,
Briggs Steven L.,
McAllister Kelly A.,
Fischl Anthony S.,
Zhao Genshi
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.20.5281
Subject(s) - biology , acyl carrier protein , transferase , biochemistry , biosynthesis , bacillus subtilis , active site , fatty acid synthase , atp synthase , enzyme , fatty acid synthesis , stereochemistry , bacteria , chemistry , genetics
Acyl carrier protein synthase (AcpS) catalyzes the formation of holo‐ACP, which mediates the essential transfer of acyl fatty acid intermediates during the biosynthesis of fatty acids and lipids in the cell. Thus, AcpS plays an important role in bacterial fatty acid and lipid biosynthesis, making it an attractive target for therapeutic intervention. We have determined, for the first time, the crystal structure of the Streptococcus pneumoniae AcpS and AcpS complexed with 3′5′‐ADP, a product of AcpS, at 2.0 and 1.9 Å resolution, respectively. The crystal structure reveals an α/β fold and shows that AcpS assembles as a tightly packed functional trimer, with a non‐crystallographic pseudo‐symmetric 3‐fold axis, which contains three active sites at the interface between protomers. Only two active sites are occupied by the ligand molecules. Although there is virtually no sequence similarity between the S.pneumoniae AcpS and the Bacillus subtilis Sfp transferase, a striking structural similarity between both enzymes was observed. These data provide a starting point for structure‐based drug design efforts towards the identification of AcpS inhibitors with potent antibacterial activity.