1FTF

CRYSTAL STRUCTURE OF STREPTOCOCCUS PNEUMONIAE ACYL CARRIER PROTEIN SYNTHASE (NATIVE 2)

Summary for 1FTF

• Entry DOI: 10.2210/pdb1ftf/pdb
• Descriptor: ACYL CARRIER PROTEIN SYNTHASE (2 entities in total)
• Functional Keywords: bacterial fatty acid biosynthesis, acyl carrier synthase, coenzyme a, structure-based drug design, transferase
• Biological source: Streptococcus pneumoniae
• Cellular location: Cytoplasm (By similarity): P0A2W6
• Total number of polymer chains: 3
• Total formula weight: 41035.52

Authors

Chirgadze, N.,Briggs, S.,McAllister, K.,Fischl, A.,Zhao, G. (deposition date: 2000-09-12, release date: 2001-09-12, Last modification date: 2023-08-09)

Primary citation

Chirgadze, N.Y.,Briggs, S.L.,McAllister, K.A.,Fischl, A.S.,Zhao, G.
Crystal structure of Streptococcus pneumoniae acyl carrier protein synthase: an essential enzyme in bacterial fatty acid biosynthesis.
EMBO J., 19:5281-5287, 2000

PubMed Abstract: 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 A resolution, respectively. The crystal structure reveals an alpha/beta 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.

PubMed: 11032795
DOI: 10.1093/emboj/19.20.5281

Experimental method

X-RAY DIFFRACTION (2.05 Å)