Application | Comment | Organism |
---|---|---|
medicine | PGT activity can be a useful target for antibiotic therapies because the enzymatic site of the enzyme is highly conserved and inhibition of PGT activity results in the inhibition of bacterial growth | Escherichia coli |
Cloned (Comment) | Organism |
---|---|
enzyme overexpression in Escherichia coli imp mutant strain | Escherichia coli |
Protein Variants | Comment | Organism |
---|---|---|
additional information | ponA is synthesized with the addition of ribosome binding site (AGGAGGT) and linker (AAAACAT) upstream of the Met1 codon. This construct is inserted at the XbaI and HindIII sites of pACT3 (21), generating pMCC1, with PBP1a expression under control of the tac promoter. pMCC1 and pACT3 are transformed into hyperpermeable Escherichia coli isolate generating CBS-3546 and CBS-3567, respectively | Escherichia coli |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
4-[3-amino-3-([1,1'-biphenyl]-4-yl)propanamido]-1,5-anhydro-2,4-dideoxy-3-O-[2-deoxy-2-({[3-(trifluoromethyl)phenyl]carbamoyl}amino)-beta-D-glucopyranosyl]-2-({[3-(trifluoromethyl)phenyl]carbamoyl}amino)-D-galactitol | - |
Escherichia coli | |
4-[3-amino-3-([1,1'-biphenyl]-4-yl)propanamido]-1,5-anhydro-2,4-dideoxy-3-O-[2-deoxy-2-({[3-(trifluoromethyl)phenyl]carbamoyl}amino)-beta-D-glucopyranosyl]-2-({[3-(trifluoromethyl)phenyl]carbamoyl}amino)-D-galactitol | - |
Staphylococcus aureus | |
ACL19098 | - |
Escherichia coli | |
ACL19098 | - |
Staphylococcus aureus | |
ACL19109 | - |
Escherichia coli | |
ACL19109 | - |
Staphylococcus aureus | |
ACL19110 | - |
Escherichia coli | |
ACL19110 | - |
Staphylococcus aureus | |
ACL19243 | - |
Escherichia coli | |
ACL19243 | - |
Staphylococcus aureus | |
ACL19273 | - |
Escherichia coli | |
ACL19273 | - |
Staphylococcus aureus | |
ACL19336 | - |
Escherichia coli | |
ACL19336 | - |
Staphylococcus aureus | |
mersacidin | a lantibiotic | Escherichia coli | |
mersacidin | a lantibiotic | Staphylococcus aureus | |
moenomycin A | moenomycins are phosphoglycolipid antibiotics that directly bind to PGT enzymes. Moenomycins are produced by certain Streptomyces species as a complex of related compounds in which moenomycin A is the major form | Escherichia coli | |
moenomycin A | moenomycins are phosphoglycolipid antibiotics that directly bind to PGT enzymes. Moenomycins are produced by certain Streptomyces species as a complex of related compounds in which moenomycin A is the major form | Staphylococcus aureus | |
additional information | molecular docking and modelling study using the structure of PBP1b, PDB ID 3VMA. NMR and mass spectrometric analysis of enzyme-inhibitor binding; PGT enzymes can be inhibited directly by compounds binding to the enzyme and indirectly by compounds binding to the lipid II substrate. Development of glycosyltransferase enzymatic activity and binding assays using the natural products moenomycin and vancomycin as model inhibitors. Design of a library of disaccharide compounds based on the minimum moenomycin fragment with peptidoglycan glycosyltransferase inhibitory activity and based on a more drug-like and synthetically versatile disaccharide building block. A subset of these disaccharide compounds bind and inhibit the glycosyltransferase enzyme. Inhibitor-enzyme binding structure analysis by 1H NMR spectral data and using crystal structure PDB ID 3VMA. MIC values with strain imp mutant BAS849 | Escherichia coli | |
additional information | molecular docking and modelling study using the structure of MGT, PDB ID 3HZS. NMR and mass spectrometric analysis of enzyme-inhibitor binding. IC50 Inhibitory curves for MGT against moenomycin complex and vancomycin, overview; PGT enzymes can be inhibited directly by compounds binding to the enzyme and indirectly by compounds binding to the lipid II substrate. Development of glycosyltransferase enzymatic activity and binding assays using the natural products moenomycin and vancomycin as model inhibitors. Design of a library of disaccharide compounds based on the minimum moenomycin fragment with peptidoglycan glycosyltransferase inhibitory activity and based on a more drug-like and synthetically versatile disaccharide building block. A subset of these disaccharide compounds bind and inhibit the glycosyltransferase enzyme. Inhibitor-enzyme binding structure analysis by 1H NMR spectral data and using crystal structure PDB ID 3HZS. MIC values with strain ATCC 29213 | Staphylococcus aureus | |
TS30153 | - |
Escherichia coli | |
TS30153 | - |
Staphylococcus aureus | |
Vancomycin | a glycopeptide | Escherichia coli | |
Vancomycin | a glycopeptide | Staphylococcus aureus |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.002 | - |
GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenol | lipid II, pH 7.5, 25°C | Escherichia coli | |
0.002 | - |
GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenol | lipid II, pH 8.0, 20°C | Staphylococcus aureus |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cell surface | - |
Staphylococcus aureus | 9986 | - |
cell surface | - |
Escherichia coli | 9986 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Ca2+ | required | Escherichia coli | |
Mn2+ | required | Staphylococcus aureus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
[GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)]n-diphosphoundecaprenol + GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenol | Staphylococcus aureus | i.e. lipid II | [GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)]n+1-diphosphoundecaprenol + undecaprenyl diphosphate | - |
? | |
[GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)]n-diphosphoundecaprenol + GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenol | Escherichia coli | i.e. lipid II | [GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)]n+1-diphosphoundecaprenol + undecaprenyl diphosphate | - |
? | |
[GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)]n-diphosphoundecaprenol + GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenol | Escherichia coli imp | i.e. lipid II | [GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)]n+1-diphosphoundecaprenol + undecaprenyl diphosphate | - |
? | |
[GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)]n-diphosphoundecaprenol + GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenol | Staphylococcus aureus ATCC 29213 | i.e. lipid II | [GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)]n+1-diphosphoundecaprenol + undecaprenyl diphosphate | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Escherichia coli | - |
- |
- |
Escherichia coli imp | - |
- |
- |
Staphylococcus aureus | - |
- |
- |
Staphylococcus aureus | - |
MRSA | - |
Staphylococcus aureus ATCC 29213 | - |
- |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | development of glycosyltransferase enzymatic activity and binding assays using the natural products moenomycin and vancomycin as model inhibitors | Staphylococcus aureus | ? | - |
? | |
additional information | NMR and mass spectrometric analysis of enzyme-substrate binding | Staphylococcus aureus | ? | - |
? | |
additional information | NMR and mass spectrometric analysis of enzyme-substrate binding | Escherichia coli | ? | - |
? | |
additional information | PGT enzymes contain two substrate binding pockets flanking the enzymatic center. For a PGT enzyme in the process of extending the peptidoglycan chain, lipid II occupies the acceptor site, and the growing chain occupies the donor site and may extend through the enzyme's exit tunnel. Each round of catalysis results in the extension of the peptidoglycan chain by two saccharides and in the release of undecaprenyl diphosphate. Development of glycosyltransferase enzymatic activity and binding assays using the natural products moenomycin and vancomycin as model inhibitors | Escherichia coli | ? | - |
? | |
additional information | NMR and mass spectrometric analysis of enzyme-substrate binding | Escherichia coli imp | ? | - |
? | |
additional information | PGT enzymes contain two substrate binding pockets flanking the enzymatic center. For a PGT enzyme in the process of extending the peptidoglycan chain, lipid II occupies the acceptor site, and the growing chain occupies the donor site and may extend through the enzyme's exit tunnel. Each round of catalysis results in the extension of the peptidoglycan chain by two saccharides and in the release of undecaprenyl diphosphate. Development of glycosyltransferase enzymatic activity and binding assays using the natural products moenomycin and vancomycin as model inhibitors | Escherichia coli imp | ? | - |
? | |
additional information | development of glycosyltransferase enzymatic activity and binding assays using the natural products moenomycin and vancomycin as model inhibitors | Staphylococcus aureus ATCC 29213 | ? | - |
? | |
additional information | NMR and mass spectrometric analysis of enzyme-substrate binding | Staphylococcus aureus ATCC 29213 | ? | - |
? | |
[GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)]n-diphosphoundecaprenol + GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenol | i.e. lipid II | Staphylococcus aureus | [GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)]n+1-diphosphoundecaprenol + undecaprenyl diphosphate | - |
? | |
[GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)]n-diphosphoundecaprenol + GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenol | i.e. lipid II | Escherichia coli | [GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)]n+1-diphosphoundecaprenol + undecaprenyl diphosphate | - |
? | |
[GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)]n-diphosphoundecaprenol + GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenol | i.e. lipid II | Escherichia coli imp | [GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)]n+1-diphosphoundecaprenol + undecaprenyl diphosphate | - |
? | |
[GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)]n-diphosphoundecaprenol + GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenol | i.e. lipid II | Staphylococcus aureus ATCC 29213 | [GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)]n+1-diphosphoundecaprenol + undecaprenyl diphosphate | - |
? |
Synonyms | Comment | Organism |
---|---|---|
bacterial cell wall glycosyltransferase | - |
Staphylococcus aureus |
bacterial cell wall glycosyltransferase | - |
Escherichia coli |
bifunctional penicillin-binding protein | - |
Staphylococcus aureus |
bifunctional penicillin-binding protein | - |
Escherichia coli |
MGT | - |
Staphylococcus aureus |
monofunctional glycosyltransferase | - |
Staphylococcus aureus |
monofunctional glycosyltransferase | - |
Escherichia coli |
PBP1a | - |
Escherichia coli |
PBP1b | - |
Escherichia coli |
PBP1c | - |
Escherichia coli |
peptidoglycan transglycosylase | - |
Staphylococcus aureus |
peptidoglycan transglycosylase | - |
Escherichia coli |
PGT | - |
Staphylococcus aureus |
PGT | - |
Escherichia coli |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
20 | - |
assay at | Staphylococcus aureus |
25 | - |
assay at | Staphylococcus aureus |
25 | - |
assay at | Escherichia coli |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.5 | - |
assay at | Staphylococcus aureus |
7.5 | - |
assay at | Escherichia coli |
8 | - |
assay at | Staphylococcus aureus |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0000076 | - |
pH 8.0, 20°C | Staphylococcus aureus | moenomycin A | |
0.00054 | - |
pH 7.5, 25°C | Escherichia coli | Vancomycin | |
0.000685 | - |
pH 8.0, 20°C | Staphylococcus aureus | Vancomycin | |
0.0062 | - |
pH 7.5, 25°C | Escherichia coli | ACL19098 | |
0.0062 | - |
pH 7.5, 25°C, PBP1b | Escherichia coli | ACL19098 | |
0.0073 | - |
pH 8.0, 20°C | Staphylococcus aureus | ACL19098 | |
0.0073 | - |
pH 7.5, 25°C, MGT | Staphylococcus aureus | ACL19098 | |
0.019 | - |
pH 7.5, 25°C | Escherichia coli | moenomycin A | |
0.0346 | - |
pH 7.5, 25°C | Escherichia coli | ACL19109 | |
0.0346 | - |
pH 7.5, 25°C, PBP1b | Escherichia coli | ACL19109 | |
0.0362 | - |
pH 7.5, 25°C | Escherichia coli | ACL19336 | |
0.0362 | - |
pH 7.5, 25°C, PBP1b | Escherichia coli | ACL19336 | |
0.0365 | - |
pH 7.5, 25°C | Escherichia coli | ACL19110 | |
0.0365 | - |
pH 7.5, 25°C, PBP1b | Escherichia coli | ACL19110 | |
0.0382 | - |
pH 8.0, 20°C | Staphylococcus aureus | ACL19109 | |
0.0382 | - |
pH 7.5, 25°C, MGT | Staphylococcus aureus | ACL19109 | |
0.04 | - |
pH 7.5, 25°C | Escherichia coli | ACL19273 | |
0.04 | - |
pH 7.5, 25°C, PBP1b | Escherichia coli | ACL19273 | |
0.0497 | - |
pH 7.5, 25°C | Escherichia coli | ACL19243 | |
0.0497 | - |
pH 7.5, 25°C, PBP1b | Escherichia coli | 4-[3-amino-3-([1,1'-biphenyl]-4-yl)propanamido]-1,5-anhydro-2,4-dideoxy-3-O-[2-deoxy-2-({[3-(trifluoromethyl)phenyl]carbamoyl}amino)-beta-D-glucopyranosyl]-2-({[3-(trifluoromethyl)phenyl]carbamoyl}amino)-D-galactitol | |
0.05 | - |
pH 8.0, 20°C | Staphylococcus aureus | ACL19273 | |
0.05 | - |
pH 7.5, 25°C, MGT | Staphylococcus aureus | ACL19273 | |
0.0732 | - |
pH 8.0, 20°C | Staphylococcus aureus | ACL19243 | |
0.0732 | - |
pH 7.5, 25°C, MGT | Staphylococcus aureus | 4-[3-amino-3-([1,1'-biphenyl]-4-yl)propanamido]-1,5-anhydro-2,4-dideoxy-3-O-[2-deoxy-2-({[3-(trifluoromethyl)phenyl]carbamoyl}amino)-beta-D-glucopyranosyl]-2-({[3-(trifluoromethyl)phenyl]carbamoyl}amino)-D-galactitol | |
0.075 | - |
pH 8.0, 20°C | Staphylococcus aureus | ACL19336 | |
0.075 | - |
pH 7.5, 25°C, MGT | Staphylococcus aureus | ACL19336 | |
0.0905 | - |
pH 8.0, 20°C | Staphylococcus aureus | ACL19110 | |
0.0905 | - |
pH 7.5, 25°C, MGT | Staphylococcus aureus | ACL19110 |
General Information | Comment | Organism |
---|---|---|
evolution | proteins with PGT activity occur as monofunctional glycosyltransferases (MGTs) and as bifunctional penicillin-binding proteins (PBPs) designated as class A PBPs | Staphylococcus aureus |
evolution | proteins with PGT activity occur as monofunctional glycosyltransferases (MGTs) and as bifunctional penicillin-binding proteins (PBPs) designated as class A PBPs | Escherichia coli |
evolution | proteins with PGT activity occur as monofunctional glycosyltransferases (MGTs) and as bifunctional penicillin-binding proteins (PBPs) designated as class A PBPs. Both forms contain a single transmembrane span at the N-terminus followed by the glycosyltransferase domain. In the class A PBPs, the C-terminus contains the transpeptidase domain. Bacterial species typically have multiple forms of these enzymes. Escherichia coli has 3 class A PBPs (PBP1a, PBP1b, and PBP1c) and 2 MGT proteins | Escherichia coli |
evolution | proteins with PGT activity occur as monofunctional glycosyltransferases (MGTs) and as bifunctional penicillin-binding proteins (PBPs) designated as class A PBPs. Both forms contain a single transmembrane span at the N-terminus followed by the glycosyltransferase domain. In the class A PBPs, the C-terminus contains the transpeptidase domain. Bacterial species typically have multiple forms of these enzymes. Staphylococcus aureus has a single class A PBP (PBP2) and 2 MGT proteins (SgtA, SgtB/MGT) | Staphylococcus aureus |
physiological function | synthesis of bacterial cell wall requires the concerted action of peptidoglycan glycosyltransferases (PGT, also known as peptidoglycan transglycosylases) and transpeptidases. The PGT enzymes transfer the disaccharide-peptide from the lipid II substrate onto the growing glycan chain allowing TP enzymes to crosslink peptides from adjacent chains. The lipid II substrate is anchored into the cell membrane through an undecaprenyl (C55) tail. Each round of catalysis results in the extension of the peptidoglycan chain by two saccharides and in the release of undecaprenyl diphosphate (C55PP) | Staphylococcus aureus |
physiological function | synthesis of bacterial cell wall requires the concerted action of peptidoglycan glycosyltransferases (PGT, also known as peptidoglycan transglycosylases) and transpeptidases. The PGT enzymes transfer the disaccharide-peptide from the lipid II substrate onto the growing glycan chain allowing TP enzymes to crosslink peptides from adjacent chains. The lipid II substrate is anchored into the cell membrane through an undecaprenyl (C55) tail. Each round of catalysis results in the extension of the peptidoglycan chain by two saccharides and in the release of undecaprenyl diphosphate (C55PP) | Escherichia coli |
physiological function | the PGT enzymes transfer the disaccharide-peptide from the lipid II substrate onto the growing glycan chain allowing transpeptidase enzymes to crosslink peptides from adjacent chains. The lipid II substrate is anchored into the cell membrane through an undecaprenyl (C55) tail. The enzymatic reaction is thought to occur at the surface of the membrane | Staphylococcus aureus |
physiological function | the PGT enzymes transfer the disaccharide-peptide from the lipid II substrate onto the growing glycan chain allowing transpeptidase enzymes to crosslink peptides from adjacent chains. The lipid II substrate is anchored into the cell membrane through an undecaprenyl (C55) tail. The enzymatic reaction is thought to occur at the surface of the membrane | Escherichia coli |