4Z19

Crystal structure of beta-ketoacyl-ACP synthase III (FabH) from Yersinia pestis with acetylated active site cysteine

Summary for 4Z19

• Entry DOI: 10.2210/pdb4z19/pdb
• Descriptor: 3-oxoacyl-[acyl-carrier-protein] synthase 3, GLYCEROL (3 entities in total)
• Functional Keywords: fabh, fatty acid biosynthesis, condensing enzyme, thiolase fold, acetylated, transferase
• Biological source: Yersinia pestis
• Cellular location: Cytoplasm : Q8ZFT7
• Total number of polymer chains: 1
• Total formula weight: 34027.57

Authors

Nanson, J.D.,Forwood, J.K. (deposition date: 2015-03-27, release date: 2015-05-20, Last modification date: 2024-10-09)

Primary citation

Nanson, J.D.,Himiari, Z.,Swarbrick, C.M.,Forwood, J.K.
Structural Characterisation of the Beta-Ketoacyl-Acyl Carrier Protein Synthases, FabF and FabH, of Yersinia pestis.
Sci Rep, 5:14797-14797, 2015

PubMed Abstract: Yersinia pestis, the causative agent of bubonic, pneumonic, and septicaemic plague, remains a major public health threat, with outbreaks of disease occurring in China, Madagascar, and Peru in the last five years. The existence of multidrug resistant Y. pestis and the potential of this bacterium as a bioterrorism agent illustrates the need for new antimicrobials. The β-ketoacyl-acyl carrier protein synthases, FabB, FabF, and FabH, catalyse the elongation of fatty acids as part of the type II fatty acid biosynthesis (FASII) system, to synthesise components of lipoproteins, phospholipids, and lipopolysaccharides essential for bacterial growth and survival. As such, these enzymes are promising targets for the development of novel therapeutic agents. We have determined the crystal structures of the Y. pestis β-ketoacyl-acyl carrier protein synthases FabF and FabH, and compared these with the unpublished, deposited structure of Y. pestis FabB. Comparison of FabB, FabF, and FabH provides insights into the substrate specificities of these enzymes, and investigation of possible interactions with known β-ketoacyl-acyl carrier protein synthase inhibitors suggests FabB, FabF and FabH may be targeted simultaneously to prevent synthesis of the fatty acids necessary for growth and survival.

PubMed: 26469877
DOI: 10.1038/srep14797

Experimental method

X-RAY DIFFRACTION (1.8 Å)