The enzyme is part of the fatty acid synthase (FAS) II system of mycobacteria, which extends modified products of the FAS I system, eventually forming meromycolic acids that are incorporated into mycolic acids. Meromycolic acids consist of a long chain, typically 50-60 carbons, which is functionalized by different groups.Two 3-oxoacyl-(acyl carrier protein) synthases function within the FAS II system, encoded by the kasA and kasB genes. The two enzymes share some sequence identity but function independently on separate sets of substrates. KasB differs from KasA (EC 2.3.1.293, meromycolic acid 3-oxoacyl-(acyl carrier protein) synthase I), by preferring longer substrates (closer to the upper limit), which also contain two double bonds.
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The enzyme appears in viruses and cellular organisms
an ultra-long-chain di-unsaturated acyl-[acyl-carrier protein] + a malonyl-[acyl-carrier protein] = an ultra-long-chain di-unsaturated 3-oxo-fatty acyl-[acyl-carrier protein] + CO2 + a holo-[acyl-carrier protein]
The enzyme is part of the fatty acid synthase (FAS) II system of mycobacteria, which extends modified products of the FAS I system, eventually forming meromycolic acids that are incorporated into mycolic acids. Meromycolic acids consist of a long chain, typically 50-60 carbons, which is functionalized by different groups.Two 3-oxoacyl-(acyl carrier protein) synthases function within the FAS II system, encoded by the kasA and kasB genes. The two enzymes share some sequence identity but function independently on separate sets of substrates. KasB differs from KasA (EC 2.3.1.293, meromycolic acid 3-oxoacyl-(acyl carrier protein) synthase I), by preferring longer substrates (closer to the upper limit), which also contain two double bonds.
the beta-ketoacyl acyl carrier protein synthase II is a mycobacterial elongation condensing enzyme involved in FAS-II, FAS-II is considered to elongate medium chain length fatty acyl primers to provide long chain, C56, precursors of mycolic acids, mycolic acids are long chain alpha-alkyl branched, beta-hydroxy fatty acids that represent a characteristic component of the Mycobacterium tuberculosis cell wall
the beta-ketoacyl acyl carrier protein synthase II is a mycobacterial elongation condensing enzyme involved in FAS-II, FAS-II is considered to elongate medium chain length fatty acyl primers to provide long chain, C56, precursors of mycolic acids, mycolic acids are long chain alpha-alkyl branched, beta-hydroxy fatty acids that represent a characteristic component of the Mycobacterium tuberculosis cell wall
the beta-ketoacyl acyl carrier protein synthase II is a mycobacterial elongation condensing enzyme involved in FAS-II, FAS-II is considered to elongate medium chain length fatty acyl primers to provide long chain, C56, precursors of mycolic acids, mycolic acids are long chain alpha-alkyl branched, beta-hydroxy fatty acids that represent a characteristic component of the Mycobacterium tuberculosis cell wall
the beta-ketoacyl acyl carrier protein synthase II is a mycobacterial elongation condensing enzyme involved in FAS-II, FAS-II is considered to elongate medium chain length fatty acyl primers to provide long chain, C56, precursors of mycolic acids, mycolic acids are long chain alpha-alkyl branched, beta-hydroxy fatty acids that represent a characteristic component of the Mycobacterium tuberculosis cell wall
an inactive enzyme-deficient mutant has less density of mycolic acid, embedded in periplasmic space, with normal thickness in the cell envelope, which results in loss of acid-fastness
enzyme gene deletion in Mycobacterium tuberculosis causes loss of acid-fastness and subclinical latent tuberculosis in immunocompetent mice. An additional outcome of enzyme gene deletion is the loss of ketomycolic acid trans-cyclopropanation and a drastic reduction in methoxymycolic acid trans-cyclopropanation. Although deletion of the enzyme also markedly alters the colony morphology and abolishes classic serpentine growth (cording), the most profound effect of enzyme gene deletion is the ability of the mutant strain to persist in infected immunocompetent mice for up to 600 days without causing disease or mortality
enzyme mutants exhibit strikingly altered cell wall permeability, leading to a marked increase in susceptibility to lipophilic antibiotics and the host antimicrobial molecules defensing and lysozyme. The predominant chain lengths are 2-4 carbons shorter for oxygenated mycolates in the absence of the enzyme
an inactive enzyme-deficient mutant has less density of mycolic acid, embedded in periplasmic space, with normal thickness in the cell envelope, which results in loss of acid-fastness
enzyme mutants exhibit strikingly altered cell wall permeability, leading to a marked increase in susceptibility to lipophilic antibiotics and the host antimicrobial molecules defensing and lysozyme. The predominant chain lengths are 2-4 carbons shorter for oxygenated mycolates in the absence of the enzyme
when enzyme KasB is coexpressed with KasA, it appears to be capable of facilitating the production of lipids of the length of full meromycolic acids. KasB therefore may accept primers directly from KasA that average 40 carbons in length. KasA and KasB thus function in tandem to carrier out acyl chain elongation to achieve meromycolic acid synthesis from acyl primers provided by type I fatty acid synthase system
when enzyme KasB is coexpressed with KasA, it appears to be capable of facilitating the production of lipids of the length of full meromycolic acids. KasB therefore may accept primers directly from KasA that average 40 carbons in length. KasA and KasB thus function in tandem to carrier out acyl chain elongation to achieve meromycolic acid synthesis from acyl primers provided by type I fatty acid synthase system
enzyme-dependent mycolate elongation is essential for cording and cell wall impermeability. Enzyme-dependent cell wall impermeability is essential for antibiotic resistance. The enzyme is essential for resistance to macrophage antimicrobial activity
enzyme-dependent mycolate elongation is essential for cording and cell wall impermeability. Enzyme-dependent cell wall impermeability is essential for antibiotic resistance. The enzyme is essential for resistance to macrophage antimicrobial activity
homodimer, crystal structure, mtKasB adopts a thiolase fold but contains unique structural features in the capping region that may be crucial to its preference for longer fatty acyl chains than its counterparts from other bacteria, residues 1-260 and 261-415 form topologically equivalent N and C-terminal betaalphabetaalphabetaalphabetabeta motifs, overview, structure comparisons
homodimer, crystal structure, mtKasB adopts a thiolase fold but contains unique structural features in the capping region that may be crucial to its preference for longer fatty acyl chains than its counterparts from other bacteria, residues 1-260 and 261-415 form topologically equivalent N and C-terminal betaalphabetaalphabetaalphabetabeta motifs, overview, structure comparisons
phosphorylation of the enzyme at Thr334 and Thr336 profoundly decreases the condensing activity of the enzyme. Phosphorylation of the enzyme leads to increased cell wall permeability
phosphorylation of the enzyme at Thr334 and Thr336 profoundly decreases the condensing activity of the enzyme. Phosphorylation of the enzyme leads to increased cell wall permeability
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in complex with palmitoyl-CoA, sitting drop vapor diffusion method, using 100 mM CAPS pH 10.5, 20 % w/v PEG 8000, 200 mM NaCl, spermine hydrochloride and foscholine-9
purified recombinant enzyme, sitting drop vapour diffusion method, from 100 mM Caps, pH 10.5, 20% w/v PEG 8000, 200 mM NaCl, and 5 mM C16-CoA, with spermidine-HCl and Foscholine-9 detergent added, X-ray diffraction crystal structure determination and analysis at 2.4-3.0 A resolution, molecular replacement, structure modeling
the phosphomimetic mutant exhibits loss of acid-fast staining and is more susceptible to isoniazid, ethionamide and rifampicin compared to the wild type enzyme
the phosphomimetic mutant exhibits loss of acid-fast staining and is more susceptible to isoniazid, ethionamide and rifampicin compared to the wild type enzyme
The Mycobacterium tuberculosis FAS-II condensing enzymes Their role in mycolic acid biosynthesis, acid-fastness, pathogenesis and in future drug development