3163-37-9Relevant articles and documents
Characterization of homologous sphingosine-1- phosphate lyase isoforms in the bacterial pathogen Burkholderia pseudomallei
McLean, Christopher J.,Marles-Wright, Jon,Custodio, Rafael,Lowther, Jonathan,Kennedy, Amanda J.,Pollock, Jacob,Clarke, David J.,Brown, Alan R.,Campopiano, Dominic J.
, p. 137 - 150 (2017/01/25)
Sphingolipids (SLs) are ubiquitous elements in eukaryotic membranes and are also found in some bacterial and viral species. As well as playing an integral structural role, SLs also act as potent signaling molecules involved in numerous cellular pathways and have been linked to many human diseases. A central SL signaling molecule is sphingosine-1-phosphate (S1P), whose breakdown is catalyzed by S1P lyase (S1PL), a pyridoxal 5?-phosphate (PLP)-dependent enzyme that catalyzes the cleavage of S1P to (2E)-hexadecenal (2E-HEX) and phosphoethanolamine. Here, we show that the pathogenic bacterium, Burkholderia pseudomallei K96243, encodes two homologous proteins (S1PL2021 and S1PL2025) that display moderate sequence identity to known eukaryotic and prokaryotic S1PLs. Using an established MS-based methodology, we show that recombinant S1PL2021 is catalytically active. We also used recombinant human fatty aldehyde dehydrogenase to develop a spectrophotometric enzymecoupled assay to detect 2E-HEX formation and measure the kinetic constants of the two B. pseudomallei S1PL isoforms. Furthermore, we determined the X-ray crystal structure of the PLP-bound form of S1PL2021 at 2.1 ? resolution revealing that the enzyme displays a conserved structural fold and active site architecture comparable with known S1PLs. The combined data suggest that B. pseudomallei has the potential to degrade host SLs in a S1PL-dependent manner.-McLean, C., J. Marles-Wright, R. Custodio, J. Lowther, A. J. Kennedy, J. Pollock, D. J. Clarke, A. R. Brown, and D. J. Campopiano. Characterization of homologous sphingosine-1-phosphate lyase isoforms in the bacterial pathogen Burkholderia pseudomallei.
Oxidation of plasmalogen, low-density lipoprotein and raw 264.7 cells by photoactivatable atomic oxygen precursors
Bourdillon, Max T.,Ford, Benjamin A.,Knulty, Ashley T.,Gray, Colleen N.,Zhang, Miao,Ford, David A.,McCulla, Ryan D.
, p. 386 - 393 (2014/04/03)
The oxidation of lipids by endogenous or environmental reactive oxygen species (ROS) generates a myriad of different lipid oxidation products that have important roles in disease pathology. The lipid oxidation products obtained in these reactions are dependent upon the identity of the reacting ROS. The photoinduced deoxygenation of various aromatic heterocyclic oxides has been suggested to generate ground state atomic oxygen (O[3P]) as an oxidant; however, very little is known about reactions between lipids and O(3P). To identify lipid oxidation products arising from the reaction of lipids with O(3P), photoactivatable precursors of O( 3P) were irradiated in the presence of lysoplasmenylcholine, low-density lipoprotein and RAW 264.7 cells under aerobic and anaerobic conditions. Four different aldehyde products consistent with the oxidation of plasmalogens were observed. The four aldehydes were: tetradecanal, pentadecanal, 2-hexadecenal and hexadecanal. Depending upon the conditions, either pentadecanal or 2-hexadecenal was the major product. Increased amounts of the aldehyde products were observed in aerobic conditions. The photodeoxygenation of dibenzothiophene S-oxide has been suggested to generate ground state atomic oxygen (O[3P]). The reactivity of the putative O(3P) is distinct from other reactive oxygen species (ROS) and little is known about its reactivity with lipids and other biomolecules. In this work, exposure of low-density lipoprotein (LDL) to O(3P) yielded four aldehyde products. The same aldehydes were observed after the oxidation of an isolated plasmalogen by O(3P).
