Disease relevance of lpxC

• Genetic mapping analyses placed the asmB mutations at the 2-min region of the Escherichia coli K-12 chromosome [1].
• The lpxC gene is essential in Gram-negative bacteria but absent from mammalian genomes, making it an attractive target for antibacterial drug discovery [2].
• Overlapping segments of host DNA extended rightward for as much as 26.4 kilobase pairs from the prophage insertion point (thought to be in leuA) to include all the genes through envA [3].
• By isolating transducing phages carrying various amounts of the bacterial deoxyribonucleic acid in this region, it was possible to locate the ftsZ gene between ftsA and envA [4].

High impact information on lpxC

• N-terminal amino acid sequencing of the purified protein showed that the first 20 amino acids matched the predicted envA nucleotide sequence [5].
• The envA gene of Escherichia coli has been shown previously to be essential for cell viability (Beall, B. and Lutkenhaus, J. (1987) J. Bacteriol. 169, 5408-5415), yet it encodes a protein of unknown function [5].
• One such assembly suppressor mutation, asmB1, is an allele of lpxC (envA) whose product catalyses the first rate-limiting step in the lipid A (LPS) biosynthesis pathway [6].
• Direct examination (of the LPS showed that its amounts were reduced by the asmB mutations, with asmB1 exerting a greater effect than asmB2 or asmB3 [1].
• Thus, it appears that the asmB mutations achieve mutant OmpF assembly suppression by reducing LPS levels, which in turn may alter membrane fluidity [1].

Chemical compound and disease context of lpxC

• During septum formation in a chain-forming envA mutant that is defective in the splitting process of the septum, a shift to the shorter glycan strands was detected that was not seen in wild type E. coli cells [7].

Biological context of lpxC

• Nucleotide sequence analysis showed that the asmB mutations caused a change from F-50 to S (F50S substitution) (asmB2 and asmB3) or a G210S substitution (asmB1) in EnvA [1].
• Transcriptional organization within an Escherichia coli cell division gene cluster: direction of transcription of the cell separation gene envA [8].
• Gene disruption experiments indicated that the envA gene was an essential gene [9].
• Using a novel variable-copy plasmid vector, we demonstrate that the DNA fragment containing the envA gene is not stably maintained in multiple copies [8].
• Located 299 base pairs downstream of the envA gene was an unidentified open reading frame consisting of 147 codons [9].

Associations of lpxC with chemical compounds

• The deduced 87-amino-acid sequence of the small-CRP gene (envA) contains 15 cysteine residues, a potential signal peptide, and a potential signal peptidase II-lipid modification site [10].
• In order to simplify the interpretation of our data, we have used a mutant (envA), known to have an increased permeability to several antibiotics, including erythromycin [11].
• However, these compounds, as well as fosfomycin, cycloserine, and cefoxitin, induce at concentrations at or below the MIC of a host carrying the envA-mutation, which causes a defect in the outer membrane [12].

Other interactions of lpxC

• Also located on this DNA fragment is the 3' end of the ftsA gene and the 5' end of the envA gene [13].
• Organization of genes in the ftsA-envA region of the Escherichia coli genetic map and identification of a new fts locus (ftsZ) [4].
• Transcription of envA and the upstream fts genes terminated at this terminator and was probably uncoupled from the downstream genes, including secA [9].

Analytical, diagnostic and therapeutic context of lpxC

• Sequence analysis, transcriptional organization, and insertional mutagenesis of the envA gene of Escherichia coli [9].
• Upon induction, a protein of the size of envA was highly overproduced, as judged by SDS-PAGE [5].

References