Prokaryotic Diacylglycerol Kinase and Undecaprenol Kinase

Abstract

Prokaryotic diacylglycerol kinase (DAGK) and undecaprenol kinase (UDPK) are the lone members of a family of multispan membrane enzymes that are very small, lack relationships to any other family of proteins—including water soluble kinases, and that exhibit an unusual structure and active site architecture. Escherichia coli DAGK plays an important role in recycling diacylglycerol produced as a byproduct of biosynthesis of molecules located in the periplasmic space. UDPK seems to play an analogous role in Gram-positive bacteria, where its importance is evident by the fact that UDPK is essential for biofilm formation by the oral pathogen Streptococcus mutans. DAGK has also long served as a model system for studies of membrane protein biocatalysis, folding, stability, and structure. This review explores our current understanding of the microbial physiology, enzymology, structural biology, and folding of the prokaryotic diacylglycerol kinase family, which is based on over 40 years of studies.

Conservation of the PTEN catalytic motif in the bacterial undecaprenyl pyrophosphate phosphatase, BacA/UppP

“…Unlike other polyisoprenoids, the final steps in the synthesis of dolichol involves dephosphorylation and saturation of the a-isoprene unit to yield the alcohol (Adair et al, 1984;Ekström et al, 1984;Gough & Hemming, 1970;Skorupinska-Tudek et al, 2008). The synthesis of a polyisoprenoid alcohol is not unique to eukaryotes in that Gram-positive bacteria also accumulate undecaprenol (Van Horn & Sanders, 2012). Various models have been proposed for these final steps in dolichol biosynthesis (Chojnacki & Dallner, 1988).…”

“…Undecaprenyl pyrophosphate and dolichol de novo synthesis are distinguished by terminal products (an isoprenyl pyrophosphate versus an alcohol) as well as the saturation state of the a-isoprene units (unsaturated versus saturated). Interestingly, unlike Gram-negative bacteria which possess undetectable levels of free undecaprenol, Gram-positive bacteria maintain a significant level of free undecaprenol, but their biosynthetic pathway remains to be determined (Van Horn & Sanders, 2012). Similar to eukaryotes which encode a DK, Gram-positive bacteria encode an undecaprenol kinase (dgkA) (Hartley et al, 2008;Jerga et al, 2007), indicating that the evolutionarily older Gram-positive bacteria can yield undecaprenyl monophosphate both through phosphorylation and more universally in all eubacteria through phosphatase activity.…”

Deciphering the Metabolism of Undecaprenyl-Phosphate: The Bacterial Cell-Wall Unit Carrier at the Membrane Frontier

“…53,65 A DgkA enzyme was first described as an ATP-dependent diacylglycerol kinase in E. coli. 115 Thus, dgkA-encoded enzymes likely evolved toward two divergent functions in bacteria, as the E. coli DgkA enzyme is specific for the diacylglycerol substrate, while the DgkA enzyme from B. subtilis and S. pneumoniae are specific for C 55 -OH. The fact that E. coli DgkA does not phosphorylate C 55 -OH is consistent with the absence of this derivative in this bacterium.…”

“…Most studies relevant to this family of enzymes were performed on diacylglycerol kinases and yet little is known about the specific properties of C 55 -OH kinases. 115 The 3D structure of the E. coli DgkA protein was determined by solution NMR spectroscopy 114 and more recently, by crystallography. 63 To what extent the structure and the catalytic mechanism of Gram-positive DgkA enzymes differ from their E. coli homologue remains to be established.…”

“…Interestingly, Gram-negative DgkA enzymes recycle diacylglycerol into phosphatidic acid that will re-enter the glycerophospholipid biosynthesis pathway. 115 The diacylglycerol appears at the outer leaflet of the plasma membrane after the transfer of a phosphoglycerol group from phosphatidylglycerol to decorate nascent LPS molecules or membrane-derived oligosaccharides (periplasmic MDO are produced in low osmolarity conditions). Then, diacylglycerol should be flipped toward the inner leaflet of the plasma membrane to be subsequently phosphorylated by DgkA.…”