2.3.2.3: lysyltransferase
This is an abbreviated version!
For detailed information about lysyltransferase, go to the full flat file.
Word Map on EC 2.3.2.3
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2.3.2.3
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aureus
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phospholipid
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lysinylated
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methicillin-resistant
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daptomycin
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lysyl-phosphatidylglycerol
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aminoacylate
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regulon
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phosphatidylethanolamine
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teichoic
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analysis
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medicine
- 2.3.2.3
- aureus
- phospholipid
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lysinylated
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methicillin-resistant
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daptomycin
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lysyl-phosphatidylglycerol
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aminoacylate
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regulon
- phosphatidylethanolamine
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teichoic
- analysis
- medicine
Reaction
Synonyms
LPG synthetase, Lys-tRNA(Lys) phosphatidylglycerol transferase, lysophosphatidylglycerol synthetase, LysX, LysX protein, lysyl-PG synthase, lysyl-transferase-lysyl-tRNA synthetase, lysyltransferase, MprF, MprF flippase, MprF protein, mprF-lysU protein, MprF2, multiple peptide resistance factor protein, phosphatidylglycerol lysyltransferase, phospholipid flippase, RimK-related lysine biosynthesis protein, Rv1640c, Tk0278, TkLysX
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General Information
General Information on EC 2.3.2.3 - lysyltransferase
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evolution
malfunction
metabolism
physiological function
additional information
according to the presence of IS6110 insertion in the NTF region, the Beijing genotype is currently divided into two subtypes. The ancient subtype is characterized with the intact NTF region, whereas modern subtype strains demonstrate the presentation of IS6110 insertion in the NTF region. The latter subtype strains can also be discriminated by the polymorphisms of mutT genes. Modern subtype is designated to Beijing monophyletic groups 3 (Bj-MG3), whereas ancient subtype is further subdivided into Bj-MG1 and Bj-MG2 based on the RD181 deletion. The strains of modern subtype constitute the majority of Beijing genotype in most regions and demonstrate an increased virulent phenotype
evolution
the enzyme belongs to the LysX family of enzymes. Analysis of the mechanism for substrate recognition and its relationship with molecular evolution among LysX family proteins, which have different substrate specificities, overview. Substrate recognition mechanism in LysX family proteins. The lysX homologues in the lysine biosynthetic gene cluster encode enzymes that possess the signature motif (Tyr175, Ile185, Thr196, and Asn250-Ala251) for the LysX/ArgX bifunctional enzyme
evolution
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the enzyme belongs to the LysX family of enzymes. Analysis of the mechanism for substrate recognition and its relationship with molecular evolution among LysX family proteins, which have different substrate specificities, overview. Substrate recognition mechanism in LysX family proteins. The lysX homologues in the lysine biosynthetic gene cluster encode enzymes that possess the signature motif (Tyr175, Ile185, Thr196, and Asn250-Ala251) for the LysX/ArgX bifunctional enzyme
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evolution
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according to the presence of IS6110 insertion in the NTF region, the Beijing genotype is currently divided into two subtypes. The ancient subtype is characterized with the intact NTF region, whereas modern subtype strains demonstrate the presentation of IS6110 insertion in the NTF region. The latter subtype strains can also be discriminated by the polymorphisms of mutT genes. Modern subtype is designated to Beijing monophyletic groups 3 (Bj-MG3), whereas ancient subtype is further subdivided into Bj-MG1 and Bj-MG2 based on the RD181 deletion. The strains of modern subtype constitute the majority of Beijing genotype in most regions and demonstrate an increased virulent phenotype
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evolution
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the enzyme belongs to the LysX family of enzymes. Analysis of the mechanism for substrate recognition and its relationship with molecular evolution among LysX family proteins, which have different substrate specificities, overview. Substrate recognition mechanism in LysX family proteins. The lysX homologues in the lysine biosynthetic gene cluster encode enzymes that possess the signature motif (Tyr175, Ile185, Thr196, and Asn250-Ala251) for the LysX/ArgX bifunctional enzyme
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evolution
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according to the presence of IS6110 insertion in the NTF region, the Beijing genotype is currently divided into two subtypes. The ancient subtype is characterized with the intact NTF region, whereas modern subtype strains demonstrate the presentation of IS6110 insertion in the NTF region. The latter subtype strains can also be discriminated by the polymorphisms of mutT genes. Modern subtype is designated to Beijing monophyletic groups 3 (Bj-MG3), whereas ancient subtype is further subdivided into Bj-MG1 and Bj-MG2 based on the RD181 deletion. The strains of modern subtype constitute the majority of Beijing genotype in most regions and demonstrate an increased virulent phenotype
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a MprF knockout mutant demonstrates a substantial increase in the phosphatidylglycerol:lysylphosphatidylglycerol ratio of the membrane
malfunction
a Mycobacterium avium lysX mutant strain undergoes a transition in phenotype by switching the carbon metabolism to beta-oxidation of fatty acids, along with accumulation of lipid inclusions. Proteins associated with intracellular survival are upregulated in the lysX mutant, even during extracellular growth, preparing bacteria for the conditions occurring inside host cells. In line with this, the lysX mutant exhibits enhanced intracellular growth in human-blood-derived monocytes
malfunction
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gain-of-function mutations in the phospholipid flippase MprF confer specific daptomycin resistance, although the T345A mutation does not alter lysyl-phosphatidylglycerol (LysPG) synthesis, LysPG translocation, or the Staphylococcus aureus cell surface charge. MprF-mediated DAP-resistance relies on a functional flippase domain and is restricted to daptomycin and a related cyclic lipopeptide antibiotic, friulimicin B. Daptomycin-resistant (DAP-R) Staphylococcus aureus mutants emerge during therapy, featuring isolates which in most cases possess point mutations in the mprF gene. T345A is a naturally occuring single nucleotide polymorphism (SNP) that can reproducibly cause daptomycin resistance, the mutation leads to weakened intramolecular domain interactions of MprF, suggesting that daptomycin and friulimicin resistance-conferring mutations may alter the substrate range of the MprF flippase to directly translocate these lipopeptide antibiotics or other membrane components with crucial roles in the activity of these antimicrobials
malfunction
identification of lysX mutants, Beijing and modern Beijing strains, genotyping, overview. Beijing family is a genotype of Mycobacterium tuberculosis that is disseminated worldwide predominating throughout East Asia, the former Soviet Union and South Africa. This family has a common spoligotype signature and lack of the region of difference (RD) 105. Clinical and epidemiological studies demonstrate that Beijing genotype strains are associated with high levels of bacterial resistance to drugs and enhanced ability to cause disease, contributing to increased transmissibility and rapid progression from infection to active disease. Evaluation of the virulence of Beijing genotype strains shows a wide range of virulence phenotypes
malfunction
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a Mycobacterium avium lysX mutant strain undergoes a transition in phenotype by switching the carbon metabolism to beta-oxidation of fatty acids, along with accumulation of lipid inclusions. Proteins associated with intracellular survival are upregulated in the lysX mutant, even during extracellular growth, preparing bacteria for the conditions occurring inside host cells. In line with this, the lysX mutant exhibits enhanced intracellular growth in human-blood-derived monocytes
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malfunction
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identification of lysX mutants, Beijing and modern Beijing strains, genotyping, overview. Beijing family is a genotype of Mycobacterium tuberculosis that is disseminated worldwide predominating throughout East Asia, the former Soviet Union and South Africa. This family has a common spoligotype signature and lack of the region of difference (RD) 105. Clinical and epidemiological studies demonstrate that Beijing genotype strains are associated with high levels of bacterial resistance to drugs and enhanced ability to cause disease, contributing to increased transmissibility and rapid progression from infection to active disease. Evaluation of the virulence of Beijing genotype strains shows a wide range of virulence phenotypes
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malfunction
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identification of lysX mutants, Beijing and modern Beijing strains, genotyping, overview. Beijing family is a genotype of Mycobacterium tuberculosis that is disseminated worldwide predominating throughout East Asia, the former Soviet Union and South Africa. This family has a common spoligotype signature and lack of the region of difference (RD) 105. Clinical and epidemiological studies demonstrate that Beijing genotype strains are associated with high levels of bacterial resistance to drugs and enhanced ability to cause disease, contributing to increased transmissibility and rapid progression from infection to active disease. Evaluation of the virulence of Beijing genotype strains shows a wide range of virulence phenotypes
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the C-terminal domain of the enzyme is responsible for the synthesis of lysylphosphatidylglycerol
metabolism
significance of lysX in the metabolism and virulence of the environmental pathogen Mycobacterium avium hominissuis
metabolism
the enzyme LysX is involved in the lysine biosynthesis pathway. The conversion from alpha-aminoadipate (AAA) to lysine, is accomplished by five enzymes: LysX, LysZ, LysY, LysJ, and LysK, using the amino group carrier protein LysW. The alpha-amino group of AAA is modified with LysW by LysX, forming an isopeptide bond between the alpha-amino group of AAA and gamma-carboxyl group of the glutamate residue at the C terminus of LysW. LysW-gamma-AAA thus synthesized is then transferred to subsequent biosynthetic enzymes to be converted to LysW-gamma-lysine by phosphorylation, reduction, and amination steps. In the final step, LysW-gamma-lysine is recognized by LysK, a carboxypeptidase, resulting in the release of lysine. LysW contains many acidic amino acid residues for electrostatic interactions with each enzyme, and, thus, functions as an amino group carrier protein for efficient lysine biosynthesis
metabolism
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the enzyme LysX is involved in the lysine biosynthesis pathway. The conversion from alpha-aminoadipate (AAA) to lysine, is accomplished by five enzymes: LysX, LysZ, LysY, LysJ, and LysK, using the amino group carrier protein LysW. The alpha-amino group of AAA is modified with LysW by LysX, forming an isopeptide bond between the alpha-amino group of AAA and gamma-carboxyl group of the glutamate residue at the C terminus of LysW. LysW-gamma-AAA thus synthesized is then transferred to subsequent biosynthetic enzymes to be converted to LysW-gamma-lysine by phosphorylation, reduction, and amination steps. In the final step, LysW-gamma-lysine is recognized by LysK, a carboxypeptidase, resulting in the release of lysine. LysW contains many acidic amino acid residues for electrostatic interactions with each enzyme, and, thus, functions as an amino group carrier protein for efficient lysine biosynthesis
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metabolism
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significance of lysX in the metabolism and virulence of the environmental pathogen Mycobacterium avium hominissuis
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metabolism
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the enzyme LysX is involved in the lysine biosynthesis pathway. The conversion from alpha-aminoadipate (AAA) to lysine, is accomplished by five enzymes: LysX, LysZ, LysY, LysJ, and LysK, using the amino group carrier protein LysW. The alpha-amino group of AAA is modified with LysW by LysX, forming an isopeptide bond between the alpha-amino group of AAA and gamma-carboxyl group of the glutamate residue at the C terminus of LysW. LysW-gamma-AAA thus synthesized is then transferred to subsequent biosynthetic enzymes to be converted to LysW-gamma-lysine by phosphorylation, reduction, and amination steps. In the final step, LysW-gamma-lysine is recognized by LysK, a carboxypeptidase, resulting in the release of lysine. LysW contains many acidic amino acid residues for electrostatic interactions with each enzyme, and, thus, functions as an amino group carrier protein for efficient lysine biosynthesis
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MprF2-mediated lysyl-phosphatidylglycerol production confers cationic antimicrobial peptide susceptibility with 6fold decreased daptomycin susceptibility or 4fold decreased gallidermin and nisin susceptibility compared to the Staphylococcus aureus mprF deletion mutant
physiological function
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enzyme MprF is a bifunctional bacterial resistance protein that synthesizes the positively charged lipid lysyl-phosphatidylglycerol (LysPG) and translocates it subsequently from the inner membrane leaflet to the outer membrane leaflet. MprF links lysine to negatively charged phosphatidylglycerol (PG) and translocates the resulting positively charged lysyl-PG (LysPG) to the outer leaflet of the cytoplasmic membrane (CM), resulting in electrostatic repulsion of cationic antimicrobial peptides (CAMPs), including human defensins and bacterial lantibiotics
physiological function
in comparison with Gram-negative bacteria, Gram-positive bacteria in general have much less zwitterionic phosphatidylethanolamine. They are known for producing aminoacylated phosphatidylglycerol (PG), especially positively charged L-lysyl-PG, which is catalyzed by lysyl-PG synthase MprF. Enzyme MprF appears to have a broad range of specificity for L-aminoacyl transfer RNAs. Lipids from Bacillus subtilis are extremely abundant in lysyl-PG and somewhat rich in alanyl-PG. It appears that N-succinylation of lipids in Bacillus subtilis strain 168 is specific to lysyl-PG but not alanyl-PG
physiological function
lysyl-phosphatidylglycerol is one of the components of the mycobacterial membrane that contributes to the resistance to cationic antimicrobial peptides, a host-induced frontline defense against invading pathogens. Its production is catalyzed by LysX, a bifunctional protein with lysyl transferase and lysyl transfer RNA synthetase activity
physiological function
Mycobacterium tuberculosis (Mtb) has developed mechanisms to avoid antimicrobial peptides (AMPs) activity, for instance lysX adds lysine residues to surface phospholipids changing their net charge, leading to the repelling of the AMPs. In the presence of AMPs, lysX expression increases significantly. Strains with higher lysX expression show increased levels of intracellular survival in vivo and in vitro and induce more severe lesion related with pneumonia. Ability of Mtb to replicate intracellularly is directly correlated to the level of lysX expression showing that the amount of lysX produced by the bacterial cell is an important variable for the modulation of Mtb virulence. Gene expression of AMPs during in vivo infection of BALB/c mice, overview
physiological function
the lysine connection with phosphatidylglycerol (PG) may alter the Mycobacterium tuberculosis surface charge, and consequently decrease the bacterial vulnerability to antimicrobial action of the immune cells. PG lysinylation plays an important role in maintaining an optimal membrane potential for Mycobacterium tuberculosis and promoting the survival of pathogen upon infection
physiological function
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in comparison with Gram-negative bacteria, Gram-positive bacteria in general have much less zwitterionic phosphatidylethanolamine. They are known for producing aminoacylated phosphatidylglycerol (PG), especially positively charged L-lysyl-PG, which is catalyzed by lysyl-PG synthase MprF. Enzyme MprF appears to have a broad range of specificity for L-aminoacyl transfer RNAs. Lipids from Bacillus subtilis are extremely abundant in lysyl-PG and somewhat rich in alanyl-PG. It appears that N-succinylation of lipids in Bacillus subtilis strain 168 is specific to lysyl-PG but not alanyl-PG
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physiological function
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lysyl-phosphatidylglycerol is one of the components of the mycobacterial membrane that contributes to the resistance to cationic antimicrobial peptides, a host-induced frontline defense against invading pathogens. Its production is catalyzed by LysX, a bifunctional protein with lysyl transferase and lysyl transfer RNA synthetase activity
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physiological function
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the lysine connection with phosphatidylglycerol (PG) may alter the Mycobacterium tuberculosis surface charge, and consequently decrease the bacterial vulnerability to antimicrobial action of the immune cells. PG lysinylation plays an important role in maintaining an optimal membrane potential for Mycobacterium tuberculosis and promoting the survival of pathogen upon infection
-
physiological function
-
Mycobacterium tuberculosis (Mtb) has developed mechanisms to avoid antimicrobial peptides (AMPs) activity, for instance lysX adds lysine residues to surface phospholipids changing their net charge, leading to the repelling of the AMPs. In the presence of AMPs, lysX expression increases significantly. Strains with higher lysX expression show increased levels of intracellular survival in vivo and in vitro and induce more severe lesion related with pneumonia. Ability of Mtb to replicate intracellularly is directly correlated to the level of lysX expression showing that the amount of lysX produced by the bacterial cell is an important variable for the modulation of Mtb virulence. Gene expression of AMPs during in vivo infection of BALB/c mice, overview
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physiological function
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the lysine connection with phosphatidylglycerol (PG) may alter the Mycobacterium tuberculosis surface charge, and consequently decrease the bacterial vulnerability to antimicrobial action of the immune cells. PG lysinylation plays an important role in maintaining an optimal membrane potential for Mycobacterium tuberculosis and promoting the survival of pathogen upon infection
-
physiological function
-
Mycobacterium tuberculosis (Mtb) has developed mechanisms to avoid antimicrobial peptides (AMPs) activity, for instance lysX adds lysine residues to surface phospholipids changing their net charge, leading to the repelling of the AMPs. In the presence of AMPs, lysX expression increases significantly. Strains with higher lysX expression show increased levels of intracellular survival in vivo and in vitro and induce more severe lesion related with pneumonia. Ability of Mtb to replicate intracellularly is directly correlated to the level of lysX expression showing that the amount of lysX produced by the bacterial cell is an important variable for the modulation of Mtb virulence. Gene expression of AMPs during in vivo infection of BALB/c mice, overview
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additional information
crystal structure analysis revealing the mechanism of substrate recognition of alpha-aminoadipate substrate by LysX and structural basis for the bifunctionality of the LysX family protein from Thermococcus kodakarensis Active site structure and reaction mechanism, structure-function analysis, detailed overview. ADP, a phosphate ion, two magnesium atoms, and the C-terminus of TkLysW-gamma-AAA are located in the active site of TkLysX
additional information
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crystal structure analysis revealing the mechanism of substrate recognition of alpha-aminoadipate substrate by LysX and structural basis for the bifunctionality of the LysX family protein from Thermococcus kodakarensis Active site structure and reaction mechanism, structure-function analysis, detailed overview. ADP, a phosphate ion, two magnesium atoms, and the C-terminus of TkLysW-gamma-AAA are located in the active site of TkLysX
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additional information
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crystal structure analysis revealing the mechanism of substrate recognition of alpha-aminoadipate substrate by LysX and structural basis for the bifunctionality of the LysX family protein from Thermococcus kodakarensis Active site structure and reaction mechanism, structure-function analysis, detailed overview. ADP, a phosphate ion, two magnesium atoms, and the C-terminus of TkLysW-gamma-AAA are located in the active site of TkLysX
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