Disease relevance of acpP

• The gene encoding Escherichia coli acyl carrier protein lies within a cluster of fatty acid biosynthetic genes [1].
• Characterization of the acyl carrier protein gene and the fab gene locus in Xanthomonas albilineans [2].
• Biochemical characterization of acyl carrier protein (AcpM) and malonyl-CoA:AcpM transacylase (mtFabD), two major components of Mycobacterium tuberculosis fatty acid synthase II [3].
• Finally, we observed that an increase in the efficiency of modification of overexpressed ACP results in decreased toxicity [4].
• We now demonstrate that the lpxA gene from Neisseria meningitidis encodes a similar acyltransferase that selectively utilizes 3-hydroxylauroyl-ACP [5].

High impact information on acpP

• Activation of Escherichia coli prohaemolysin to the mature toxin by acyl carrier protein-dependent fatty acylation [6].
• UDP-GlcNAc acyltransferase (LpxA) catalyzes the first step of lipid A biosynthesis, the transfer of the R-3-hydroxyacyl chain from R-3-hydroxyacyl acyl carrier protein (ACP) to the glucosamine 3-OH group of UDP-GlcNAc [7].
• The purified maltose binding protein-LuxI fusion protein catalyzes the synthesis of hexanoyl homoserine lactone from hexanoyl-ACP and SAM [8].
• 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 [8].
• Probing the mechanism of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III mtFabH: factors influencing catalysis and substrate specificity [9].

Chemical compound and disease context of acpP

• The two ACP species were identical but differed from the sequence reported for E. coli E-15 ACP in that an Asn instead of an Asp was at position 24 and an Ile instead of a Val was at position 43 [10].
• An isoleucine to valine substitution in Escherichia coli acyl carrier protein results in a functional protein of decreased molecular radius at elevated pH [11].
• A novel form of ACP having an increased electrophoretic mobility on polyacrylamide gel electrophoresis was noted previously during work on beta-ketoacyl-acyl carrier protein synthase II (fabF) mutants of E. coli (Jackowski, S., and Rock, C. O.(1987) J. Bacteriol. 169, 1469-1473) [11].
• 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) [12].
• Holo-acyl carrier protein synthase (ACPS) transfers the 4'-phosphopantetheine (4'-PP) moiety from coenzyme A (CoA) to Ser-36 of acyl carrier protein (ACP) in Escherichia coli [13].

Biological context of acpP

• Both ACP and F-ACP were purified to homogeneity, and their primary amino acid sequences were determined [10].
• Complementation of fabF1 mutants with an F' factor harboring the wild-type synthase II allele resulted in the appearance of normal ACP, whereas complementation with an F' possessing the fabF2 allele (a mutation that produces a synthase II enzyme with altered catalytic activity) resulted in the production of both forms of ACP [10].
• Site-directed mutagenesis of a synthetic ACP gene demonstrated that the amino acid substitution at residue 43 is the cause of the increased electrophoretic mobility [11].
• 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) [14].
• Only acyl carrier protein, not acyl-CoA, can promote HlyC-directed proHlyA acylation, but a range of acyl groups are effective [6].

Associations of acpP with chemical compounds

• The two carrier proteins of O-island 138 of strain O157:H7 are not modified (or only very poorly modified) by AcpS, the PPTase responsible for 4'-phosphopantetheine attachment to the acyl carrier protein (AcpP) of fatty acid synthesis [15].
• Moreover, on the basis of its in vitro activity, it is possible that the S. glaucescens FabD MAT is responsible for charging the TcmM ACP with malonate in vivo, a key step in the synthesis of the deca(polyketide) precursor of Tcm C [16].
• CoA is the biosynthetic precursor to the ACP prosthetic group, but apo-ACP did not accumulate when the intracellular CoA concentration was severely depressed in strain SJ16 (panD), a beta-alanine auxotroph [17].
• This mutation results in substitution of isoleucine for valine 43 of ACP [11].
• It is competitive with respect to acyl-ACP but not UDP-GlcNAc [7].

Physical interactions of acpP

• Escherichia coli LipA is a lipoyl synthase: in vitro biosynthesis of lipoylated pyruvate dehydrogenase complex from octanoyl-acyl carrier protein [18].

Other interactions of acpP

• Altered molecular form of acyl carrier protein associated with beta-ketoacyl-acyl carrier protein synthase II (fabF) mutants [10].
• By using an oligodeoxynucleotide synthesized in accordance with the sequence of residues 25-36 of the ACP, the fabC gene encoding this protein was cloned, and expression of this gene in Escherichia coli yielded the ACP entirely as the active holoenzyme [16].
• Strain MP4 (acpS) is conditionally defective in [ACP]synthase (EC 2.7.8.7) and apo-ACP was the predominant form of ACP synthesized in this strain under nonpermissive conditions [17].
• We have detected a very slow LplA-catalyzed transfer of lipoic acid and octanoic acid from their acyl carrier protein thioesters to the lipoyl domain of pyruvate dehydrogenase [19].
• Isolation and characterization of beta-ketoacyl-acyl carrier protein reductase (fabG) mutants of Escherichia coli and Salmonella enterica serovar Typhimurium [20].

Analytical, diagnostic and therapeutic context of acpP

• Gel filtration experiments indicated that the increased electrophoretic mobility results from the more compact structure of V43I ACP at high pH [11].
• Correct folding of the act ACP has been confirmed by circular dichroism (CD) and 1H NMR [21].
• 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 [22].

References