Disease relevance of LYS5

• Recombinant Lys5p expressed in Escherichia coli activates C. albicans Lys2p for the AAR activity and also activates AARs from S. cerevisiae and to a lesser extent Schizosaccharomyces pombe [1].
• Genes encoding PPTases Sfp and Gsp from Bacillus spp., which are involved in non-ribosomal peptide antibiotic synthesis, complemented the lys5 deletion, whereas ydcB of Bacillus subtilis, which encodes the acyl carrier protein synthase involved in fatty acid synthesis, could not [2].

High impact information on LYS5

• CDC42 maps distal to the rDNA on chromosome XII and CDC43 maps near lys5 on chromosome VII [3].
• The peak reversion frequency for lys5 is somewhat later, while the peaks for tyr3 and trp5 occur near the end of DNA replication [4].
• IME4 is located between ADE5 and LYS5 on chromosome VII [5].
• Mutants affected at the LYS5 locus of Yarrowia lipolytica lack detectable dehydrogenase (SDH) activity [6].
• Overlapping reading frames at the LYS5 locus in the yeast Yarrowia lipolytica [6].

Biological context of LYS5

• The cloned LYS5 gene was contained within a 7.5 kb DNA insert of the recombinant plasmid pSC5 [7].
• S1 nuclease analysis localizes the transcription initiation site relative to the detailed restriction map, and reveals the direction of transcription, as well as the transcript size of the LYS5 gene which can be no greater than 1.65 kb [8].
• Novel MX cassettes are described that contain the open reading frames (ORFs) of Saccharomyces cerevisiae or Candida albicans LYS5 [9].
• Here, we show that the 31-kDa Lys5 is a specific posttranslational modification catalyst, using coenzyme A (CoASH) as a cosubstrate to phosphopantetheinylate Ser880 of the 155-kDa Lys2 and activate it for catalysis [10].
• (B. B. Chattoo, F. Sherman, D. A. Azubalis, T. A. Fjellstedt, D. Mehnert, and M. Ogur, Genetics 93:51-65, 1979) relied on this difference in the effective utilization of alpha-aminoadipate to develop a procedure for directly selecting lys2 and lys5 mutants [11].

Associations of LYS5 with chemical compounds

• In Saccharomyces cerevisiae and Candida albicans, the LYS2-encoded AAR is posttranslationally activated by CoA and the LYS5-encoded PPTase [12].
• In Saccharomyces cerevisiae, the functions of two unlinked genes (LYS2 and LYS5) are required for the synthesis of the lysine biosynthetic enzyme, alpha-aminoadipate reductase [7].
• The alpha-aminoadipate reductase (AAR) of this pathway catalyzes the conversion of alpha-aminoadipic acid to alpha-aminoadipic-delta-semialdehyde by a complex mechanism involving two gene products, Lys2p and Lys5p [13].
• Site-directed mutational analyses reveal glutamic acid 198 in the Lys5p Core 3 as essential for the activation of recombinant Lys2p AAR activity [1].
• The apo-PCP fragment was covalently modified to phosphopantetheinylated holo-PCP by pure Lys5 and CoASH with a Km of 1 microM and kcat of 3 min-1 for both the PCP and CoASH substrates [10].

Other interactions of LYS5

• The pSC5 transformed Lys5+ cells and the wild-type strain exhibited same level of alpha-aminoadipate reductase activity, whereas lys5 mutant and plasmid-cured transformed strain exhibited none [7].
• Two yet uncharacterized fungal genes, q10474 of Schizosaccharomyces pombe, meanwhile annotated as the putative lys7 gene, and npgA of Aspergillus nidulans, also complemented the lys5 deletion and have thus been functionally characterized as PPTases [2].

Analytical, diagnostic and therapeutic context of LYS5

• Sequence alignment of Lys5p with other PPTases reveals highly conserved putative PPTase domains including the Core 3, WXXKESXXK (residues 194-202) [1].
• Both LYS1 and LYS5 DNA-specific PCR primers SG1, SG2 and SG3, SG4, respectively, amplified predicted 483 and 648-bp fragments from Candida albicans genomic DNA but not from other selected fungal, bacterial, or human DNA [14].

References