Disease relevance of ECs1472

• The presence of an ACP gene within the tcm gene cluster suggests that different ACPs are used in fatty acid and polyketide biosynthesis in Streptomyces [1].
• The deduced amino acid sequence of the mature protein is homologous to the beta-ketoacyl-[acyl carrier protein] (ACP) synthase I [3-oxoacyl-ACP synthase; acyl-ACP:malonyl-ACP C-acyltransferase (decarboxylating), EC 2.3.1.41] of Escherichia coli [2].
• Malonyl coenzyme A (CoA)-acyl carrier protein (ACP) transacylase (MCAT) is an essential enzyme in the biosynthesis of fatty acids in all bacteria, including Mycobacterium tuberculosis [3].
• Identification, substrate specificity, and inhibition of the Streptococcus pneumoniae beta-ketoacyl-acyl carrier protein synthase III (FabH) [4].
• 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 [5].

High impact information on ECs1472

• Thus, the acyl-CoA hydrolysis activity requires 4 of the 9 domains of HMWP1, and it is consistent with autoacylation of the AT domain active site serine and subsequent passage of the itinerant acyl chain from AT to ACP to PCP(3) to the TE domain, a cascade of four sequential acyl-enzyme intermediates, for hydrolytic turnover [6].
• The purified maltose binding protein-LuxI fusion protein catalyzes the synthesis of hexanoyl homoserine lactone from hexanoyl-ACP and SAM [7].
• 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 [7].
• 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 [5].
• Acyl carrier protein is a cellular target for the antibacterial action of the pantothenamide class of pantothenate antimetabolites [5].

Chemical compound and disease context of ECs1472

• ACP purified from stationary phase Escherichia coli B cells was found to exist primarily as a mixed disulfide with glutathione [8].
• UDP-N-acetylglucosamine acyltransferase of Escherichia coli catalyzes the reaction, UDP-GlcNAc + R-3-hydroxymyristoyl-ACP--> UDP-3-O-(R-3-hydroxymyristoyl)-GlcNAc + ACP [9].
• 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 [10].
• In OxyR(+) cells, where the oxidative toxicity is inhibited, DEA/NO promoted exceptional increases in the cytotoxicity of CAT and 3,4-dihydroxycinnamic (caffeic) acid (CAF), which both exhibited very low oxidative cytotoxicity, as well as in that of MCAT, HQ, and MHQ [11].
• The dpsCgene has been implicated in specifying the unique propionate-starter unit, and it encodes a protein that is very similar to the Escherichia coli beta-ketoacyl:acyl carrier protein (ACP) synthase III (FabH or KS III) enzyme of fatty acid biosynthesis [12].

Biological context of ECs1472

• Inactive ACP accumulated in pantothenamide-treated cells because of the active hydrolysis of regular ACP and the slow turnover of the inactive prosthetic group [5].
• A cDNA clone, Cs-ACP-1, encoding ACP was isolated from a coriander endosperm cDNA library [13].
• 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 [14].
• A network trained to recognize amino acid type from TOCSY data was trained on 148 assigned spin systems from E. coli acyl carrier proteins (ACPs) and tested on spin systems from spinach ACP, which has a 37% sequence homology with E. coli ACP and a similar secondary structure [15].
• 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 [16].

Associations of ECs1472 with chemical compounds

• 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 [7].
• 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) [17].
• The apparent K(m) values for acetyl-CoA and malonyl-ACP were determined to be 40.3 and 18.6 microm, respectively [4].
• 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) [17].
• The apparent Km for acyl-ACP was 13 microM, and the rate of acyl transfer from this acyl donor was enhanced by the addition of 0.4 M LiCl indicating that the exchange of enzyme-bound ACP for acyl-ACP was a determinant factor in the rate of phosphatidylethanolamine formation from acyl-ACP [18].

Analytical, diagnostic and therapeutic context of ECs1472

• The formation of ACP dimers was established by electrophoresis, gel filtration, and sedimentation equilibrium [8].
• The ACP( pool was specifically labeled in vivo with beta-[3-3H]alanine and the ACP subspecies analyzed by reversed phase liquid chromatography and conformationally sensitive gel electrophoresis [19].
• The Cs-ACP-1 mature protein was expressed in E. coli and comigrated on SDS-PAGE with the most abundant ACP expressed in endosperm tissues [13].
• Correct folding of the act ACP has been confirmed by circular dichroism (CD) and 1H NMR [20].
• An act Cys17Ser ACP was engineered by site-directed mutagenesis [21].

References