PMC

DAG kinases. (A) DgkA is the DAG kinase responsible for recycling DAG produced from the turnover of PtdGro in the synthesis of membrane-derived oligosaccharides in E. coli. DgkA is the prototypical DAG kinase of Gram-negative bacteria. It is an integral membrane protein that assembles as a trimer in the bilayer. The individual subunits of the homotrimer are colored red, green and blue. DAG enters the active site from the membrane via a gate formed by the third transmembrane domain of each subunit interacting with the first two transmembrane domains of the adjacent subunit. ATP approaches the active site from the cytosol. (B) DgkB is the DAG kinase responsible for recycling DAG produced from the synthesis of LTA in S. aureus, and is the prototypical DAG kinase of Gram-positive bacteria. DgkB is an interfacial enzyme that docks to the membrane via a positively-charged patch of amino acids located adjacent to the active site. A DgkB monomer is shown in green ribbon and ADP is shown in the structure as sticks.

Pathways for the biosynthesis of PtdOH in bacteria. (A) PtdOH metabolism in E. coli is representative of the bacteria that utilize the PlsB/PlsC acyltransferase pathway to PtdOH. These acyltransferases use either acyl-ACP substrates produced by type II fatty acid synthesis (FASII) or acyl-CoA thioesters generated by the activation of exogenous fatty acids by acyl-CoA synthetase (FadD). The PlsB pathway is largely confined to the γ-proteobacteria. (B) PtdOH metabolism in S. aureus is representative of bacteria that utilize the PlsX/PlsY/PlsC acyltransferase pathway to PtdOH. Acyl-ACP generated by FASII is either used by PlsC to acylate the 2-position of LPA or is converted by PlsX to acyl-PO₄ for incorporation into the 1-position by PlsY. This is the only pathway present in most Gram-positive pathogens. In both schemes, the G3P backbone is produced by GpsA, but may also be obtained from the environment by the GlpF/GlpK pathway. Many bacteria also have a transport system for G3P (not shown). Exogenous fatty acids are incorporated into phospholipid following their ligation to ACP by acyl-ACP synthetases (AAS). PlsB, PlsC, PlsY and GlpF are intrinsic membrane proteins. AAS, FadD and PlsX are soluble proteins that are thought to interact with the membrane interface.