Disease relevance of homoserine

• Quenching quorum-sensing-dependent bacterial infection by an N-acyl homoserine lactonase [1].
• Sensing starvation: a homoserine lactone--dependent signaling pathway in Escherichia coli [2].
• The function of homoserine lactone derivatives in many cell density-dependent phenomena and the similarity of RspA to a Streptomyces ambofaciens protein suggest that synthesis of homoserine lactone may be a general signal of starvation [2].
• A significant number of gram-negative bacteria produce acylated homoserine lactones (acyl-HSLs) as signal molecules that function in quorum sensing [3].
• N-acyl homoserine lactone binding to the CarR receptor determines quorum-sensing specificity in Erwinia [4].

Psychiatry related information on homoserine

• Self perception in bacteria: quorum sensing with acylated homoserine lactones [5].

High impact information on homoserine

• Different bacterial species may produce different AHLs, which vary in the length and substitution of the acyl chain but contain the same homoserine lactone moiety [1].
• Strain BH72 appears to be 'disarmed' compared to plant pathogens, having only a few enzymes that degrade plant cell walls; it lacks type III and IV secretion systems, related toxins and an N-acyl homoserine lactones-based communication system [6].
• A. tumefaciens regulates Ti plasmid conjugal transfer by a quorum-sensing signal, N-3-oxo-octanoyl homoserine lactone (3OC8HSL), also known as Agrobacterium autoinducer [7].
• Acyl homoserine lactones (acyl-HSLs) are important intercellular signaling molecules used by many bacteria to monitor their population density in quorum-sensing control of gene expression [8].
• H. virescens employs a constitutive enzyme of the larval gut, known trivially as canavanine hydrolase (CH), to catalyze an irreversible hydrolysis of L-canavanine to L-homoserine and hydroxyguanidine [9].

Chemical compound and disease context of homoserine

• In spite of the high level of aspartokinase, the growth of the transformed E. coli strain was severely inhibited by the addition of L-lysine but could be restored by also adding L-homoserine [10].
• Using this method, we have not determined the sizes of the functional units for different enzymatic activities on the "arom" conjugate from Euglena, a polyenzyme catalyzing five sequential reactions in the shikimic acid pathway, and on two conjugates from Escherichia coli carrying both aspartokinase and homoserine dehydrogenase activities [11].
• L-Cystathionine, L-homoserine, DL-lanthionine, L-djenkolic acid, and L-cystine are cleaved as preferred substrates by the Streptomyces enzyme [12].
• Conjugation of Agrobacterium tumefaciens wide-host-range octopine-type Ti plasmids is regulated by the LuxR-type transcriptional activator TraR in conjunction with an acylated homoserine lactone designated AAI [13].
• In cell-free Yersinia pseudotuberculosis culture supernatants, we have chemically characterized three N-acyl homoserine lactone (AHL) molecules, N-octanoyl homoserine lactone (C8-HSL), N-(3-oxohexanoyl)homoserine lactone (3-oxo-C6-HSL) and N-hexanoyl homoserine lactone (C6-HSL) [14].

Biological context of homoserine

• Many bacteria use acyl homoserine lactone signals to monitor cell density in a type of gene regulation termed quorum sensing and response [15].
• Several Pseudomonas species produce acylated homoserine lactones that control important functions including pathogenicity and plant growth promotion [16].
• We have determined that the AHL, 3-oxododecanoyl homoserine lactone (3-oxo-C12-(L)-HSL) can down-regulate thymidylate synthase protein at 10 micromol/L and reduce H630 (human colorectal cancer) growth by 50% at 23 micromol/L (IC50) in cell culture [17].
• Kinetic and regulatory mechanisms for (Escherichia coli) homoserine dehydrogenase-I. Equilibrium isotope exchange kinetics [18].
• These results suggest that the long homoserine side chain may induce an unusually large off rate for the peptide and/or may misalign the hydroxyl moiety in the active site [19].

Anatomical context of homoserine

• Sickling of erythrocytes was rapidly and quantitatively inhibited at room temperature by 3.8 mM homoserine, asparagine, and glutamine but by no other amino acid [20].
• The catalytic subunit of the cAMP-dependent protein kinase from bovine cardiac muscle phosphorylates homoserine in the synthetic peptide Leu-Arg-Arg-Ala-Hse-Leu-Gly [19].
• The Pseudomonas autoinducer, N-3-oxododecanoyl homoserine lactone (3-O-C12-HSL), is a small lipid-soluble molecule that is essential in the regulation of many P. aeruginosa virulence factors, but little is known about how it affects eukaryotic cells [21].
• IL-8 production in human lung fibroblasts and epithelial cells activated by the Pseudomonas autoinducer N-3-oxododecanoyl homoserine lactone is transcriptionally regulated by NF-kappa B and activator protein-2 [21].
• Experiments with the wild type and lasIrhlI, pqsA, pqsL and fliMpilA mutants indicated that the extracellular DNA is generated via a mechanism which is dependent on acyl homoserine lactone and Pseudomonas quinolone signalling, as well as on flagella and type IV pili [22].

Associations of homoserine with other chemical compounds

• Canaline reductase, having a mass of approximately 167 kDa and composed of 82-kDa dimers, catalyzes a NADPH-dependent reductive cleavage of L-canaline to L-homoserine and ammonia [23].
• Marked protection of the enzyme against loss of threonine sensitivity at pH 9 is afforded by MgATP-2- plus K+ and homoserine [24].
• The spectrum of the tryptic digest of native BpKatG also contained a major ion for a peptide in which Met264 had been converted to homoserine, consistent with the covalent bond between Tyr238 and Met264 being susceptible to hydrolysis, including the loss of the CH3-S from the methionine [25].
• The inhibition by L-serine of the homoserine dehydrogenase displays Michaelis-Menten kinetics which are of a competitive nature versus homoserine [26].
• Homocysteine thiolactone, selenohomocysteine lactone, and homoserine lactone were found to be competitive, irreversible inhibitors of lysyl oxidase, with KI values of 21 +/- 3 microM, 8.3 +/- 2.2 microM, and 420 +/- 56 microM, respectively [27].

Gene context of homoserine

• Mutations in HOM3 result in a requirement for threonine and methionine (or homoserine) for growth and a lack of detectable aspartokinase activity [28].
• Nucleotide sequence of the metA gene encoding homoserine trans-succinylase in Escherichia coli [29].
• Most of the mutants showed a three- to fourfold increase in homoserine dehydrogenase (thrA gene product) synthesis relative to the wild-type parent strain [30].
• Transcriptional and biochemical regulation of a novel Arabidopsis thaliana bifunctional aspartate kinase-homoserine dehydrogenase gene isolated by functional complementation of a yeast hom6 mutant [31].
• To obtain information about the possible origin of this yeast, we cloned two different S. carlsbergensis MET2 genes (encoding homoserine acetyltransferase) [32].

Analytical, diagnostic and therapeutic context of homoserine

• The apparent molecular radius of the enzyme complex as determined by gel filtration at pH 8.85 in the presence of threonine or MgATP-2- plus K+ and homoserine is dependent on the enzyme concentration [24].
• Conformationally assisted ligation of these peptides with the native cytochrome c fragment 1-65 (homoserine lactone form) occurred in high yield [33].
• Characterization of proteolysis fragments of aspartokinase I: homoserine dehydrogenase I. Fluorescence and circular dichroism studies [34].
• A gacS/gacA-dependent homoserine lactone activity as detected by bioassay was also unaffected by the disruption of salA [35].
• By using thin-layer chromatography in conjunction with high-performance liquid chromatography (HPLC) and mass spectrometry, we show that purified Rhll can catalyse the biosynthesis of BHL and HHL using either S-adenosylmethionine (SAM) or homoserine lactone (HSL) but not homoserine as the source of the homoserine lactone moiety [36].

References