Disease relevance of acpP

• AcpP peptide-PMOs targeted to acpP inhibited growth of E. coli or Salmonella enterica serovar Typhimurium to various extents, depending on the strain [1].
• Identification, substrate specificity, and inhibition of the Streptococcus pneumoniae beta-ketoacyl-acyl carrier protein synthase III (FabH) [2].
• Acyl carrier protein metabolism and regulation of fatty acid biosynthesis by Lactobacillus plantarum [3].
• Here we show that the mechanism for the toxicity of the pantothenamides is due to the inhibition of fatty acid biosynthesis through the formation and accumulation of the inactive acyl carrier protein (ACP), which was easily observed as a faster migrating protein using conformationally sensitive gel electrophoresis [4].
• The soluble acyl-acyl carrier protein synthetase of Vibrio harveyi B392 is a member of the medium chain acyl-CoA synthetase family [5].

High impact information on acpP

• This provides direct evidence that the LuxI protein is an auto-inducer synthase that catalyzes the formation of an amide bond between SAM and a fatty acyl-ACP and then catalyzes the formation of the acyl homoserine lactone from the acyl-SAM intermediate [6].
• The purified maltose binding protein-LuxI fusion protein catalyzes the synthesis of hexanoyl homoserine lactone from hexanoyl-ACP and SAM [6].
• There is a high level of specificity for hexanoyl-ACP over ACPs with differing acyl group lengths, and hexanoyl homoserine lactone was not synthesized when SAM was replaced with other amino acids, such as methionine, S-adenosylhomocysteine, homoserine, or homoserine lactone, or when hexanoyl-SAM was provided as the substrate [6].
• Acyl carrier protein is a cellular target for the antibacterial action of the pantothenamide class of pantothenate antimetabolites [4].
• Electrospray ionization time-of-flight mass spectrometry confirmed that the inactive ACP was the product of the transfer of the inactive phosphopantothenamide moiety of the CoA analog to apo-ACP, forming the ACP analog that lacks the sulfhydryl group for the attachment of acyl chains for fatty acid synthesis [4].

Chemical compound and disease context of acpP

• METHODS: An 11-base PMO (AcpP) targeted at acpP (an essential gene) of Escherichia coli was synthesized and conjugated with the cell-penetrating peptide RFFRFFRFFRXB (X is 6-aminohexanoic acid and B is beta-alanine) [7].
• Pantothenate (vitamin B5) is the precursor for the biosynthesis of the phosphopantetheine moiety of coenzyme A and acyl carrier protein, and is synthesised in Escherichia coli by four enzymic reactions [8].
• The gene encoding the unique soluble acyl-acyl carrier protein synthetase (AasS) of the bioluminescent Vibrio harveyi strain B392 has been isolated by expression cloning in Escherichia coli.This enzyme catalyzes the ATP-dependent acylation of the thiol of acyl carrier protein (ACP) with fatty acids with chain lengths from C4 to C18 [5].
• Vibrio harveyi acyl-ACP synthetase appears to be a soluble hydrophilic enzyme on the basis of subcellular fractionation and Triton X-114 phase partition assay [9].
• The cytosolic nature and enzymatic properties of V. harveyi acyl-ACP synthetase indicate that it may have a different physiological role than the membrane-bound activity of E. coli, which has been implicated in phosphatidylethanolamine turnover [9].

Biological context of acpP

• Four different bacterium-permeating peptides, RFFRFFRFFXB, RTRTRFLRRTXB, RXXRXXRXXB, and KFFKFFKFFKXB (X is 6-aminohexanoic acid and B is beta-alanine), were separately coupled to two different PMOs that are complementary to regions near the start codons of a luciferase reporter gene (luc) and a gene required for viability (acpP) [1].
• Inactive ACP accumulated in pantothenamide-treated cells because of the active hydrolysis of regular ACP and the slow turnover of the inactive prosthetic group [4].
• The Escherichia coli AcpH acyl carrier protein phosphodiesterase (also called ACP hydrolyase) is the only enzyme known to cleave a phosphodiester-linked post-translational protein modification [10].

Associations of acpP with chemical compounds

• We have demonstrated the presence of five pantothenate-containing compounds in L. plantarum which have been identified by co-chromatography with authentic samples: pantothenate, 4'-phosphopantetheine, 3'-dephosphocoenzyme A, coenzyme A, and acyl carrier protein (ACP) [3].
• Thus, the change in rate of fatty acid biosynthesis in L. plantarum upon addition of oleate to the medium can be quantitatively related to the concentration of ACP (and probably to the concentration of co-repressible enzymes of fatty acid biosynthesis) [3].
• The apparent K(m) values for acetyl-CoA and malonyl-ACP were determined to be 40.3 and 18.6 microm, respectively [2].
• Oleate in the presence of Triton X-100 was found to reduce the concentration of ACP by 80% with little effect on the concentrations of the other pantothenate-containing compounds [3].
• The acyl moiety is attached via a thioester bond to a phosphopantetheine linker that is in turn bound to a serine residue in ACP [11].

Analytical, diagnostic and therapeutic context of acpP

• An enzyme catalyzing the ligation of long chain fatty acids to bacterial acyl carrier protein (ACP) has been detected and partially characterized in cell extracts of the bioluminescent bacterium Vibrio harveyi [9].

References