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Literature summary for 2.4.1.129 extracted from
- Positive cooperativity between acceptor and donor sites of the peptidoglycan glycosyltransferase (2015), Biochem. Pharmacol., 93, 141-150.
Application
| Application | Comment | Organism |
|---|---|---|
| drug development | the essential function of the enzyme makes it an attractive antimicrobial target | Staphylococcus aureus |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| gene mtgA, recombinant expression of wild-type and mutant enzymes | Staphylococcus aureus |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| E100Q | site-directed mutagenesis, E100Q binds moenomycin A in the same order of magnitude as the wild-type | Staphylococcus aureus |
| F104A | site-directed mutagenesis, the binding response for F104A is drastically decreased compared to the wild-type | Staphylococcus aureus |
| F120S | site-directed mutagenesis, modification of the residue within the hydrophobic region of enzyme MtgA yields monodisperse forms of the protein with apparently no change in its secondary structure content, but at the expense of the enzyme function. Mutation F120S may affect the outer helix transition/conformational change during catalysis | Staphylococcus aureus |
| F150S | site-directed mutagenesis, insoluble mutant | Staphylococcus aureus |
| F158S | site-directed mutagenesis | Staphylococcus aureus |
| L112N | site-directed mutagenesis | Staphylococcus aureus |
| L119N | site-directed mutagenesis, modification of the residue within the hydrophobic region of enzyme MtgA yields monodisperse forms of the protein with apparently no change in its secondary structure content, but at the expense of the enzyme function. Mutation L119N may affect the outer helix transition/conformational change during catalysis | Staphylococcus aureus |
| L119N/F120S/E100Q | structure of MtgA in complex with moenomycin A bound to the donor site, PDB 3HZS | Staphylococcus aureus |
| V154S | site-directed mutagenesis | Staphylococcus aureus |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| (2R)-2-[[(2S)-2-([[(2R,3R,4R,5S,6R)-5-[[(2S,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy]-4-[(1S)-1-carboxyethoxy]-2-[[(hexadecyloxy)(hydroxy)phosphoryl]oxy]-6-(hydroxymethyl)oxan-3-yl]carbamoyl]amino)propanoyl]amino]pentanedioic acid | - |
Staphylococcus aureus |  |
| (2R)-2-[[(2S)-2-[[(2S)-2-[[(2R,3R,4R,5S,6R)-3-acetamido-2-([[(2R)-2-carboxy-2-(hexadecyloxy)ethoxy](hydroxy)phosphoryl]oxy)-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy]propanoyl]amino]propanoyl]amino]pentanedioic acid | - |
Staphylococcus aureus | |
| (2R)-2-[[(2S)-2-[[(2S)-2-[[(2R,3R,4R,5S,6R)-3-acetamido-2-[[(hexadecyloxy)(hydroxy)phosphoryl]oxy]-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy]propanoyl]amino]propanoyl]amino]pentanedioic acid | - |
Staphylococcus aureus | |
| (2R)-2-[[(2S)-2-[[(2S)-2-[[(2R,3S,4R,5R,6R)-3-[[(2S,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy]-5-(2-carboxyethyl)-6-([[(2R)-2-carboxy-2-(pentadecyloxy)ethoxy](hydroxy)phosphoryl]oxy)-2-(hydroxymethyl)oxan-4-yl]oxy]propanoyl]amino]propanoyl]amino]pentanedioic acid | - |
Staphylococcus aureus | |
| 2-acetamido-3-O-[(1S)-1-carboxyethyl]-1-O-[[(2R)-2-carboxy-2-(hexadecyloxy)ethoxy](hydroxy)phosphoryl]-2-deoxy-alpha-D-glucopyranose | - |
Staphylococcus aureus | |
| 2-acetamido-4-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-3-O-[(1S)-1-carboxyethyl]-2-deoxy-1-O-[(hexadecyloxy)(hydroxy)phosphoryl]-alpha-D-glucopyranose | - |
Staphylococcus aureus | |
| 4-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-2-(carboxyamino)-3-O-[(1S)-1-carboxyethyl]-1-O-[[(2R)-2-carboxy-2-(pentadecyloxy)ethoxy](hydroxy)phosphoryl]-2-deoxy-alpha-D-glucopyranose | - |
Staphylococcus aureus | |
| Moenomycin | moenomycin A inhibits the transglycosylation step by binding to the donor site of the glycosyltransferase | Staphylococcus aureus | |
| additional information | several analogues of the enzyme's lipid II substrate are synthesized previously and found to inhibit the enzyme activity in vitro and cause bacterial growth defect, overview | Staphylococcus aureus |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| peptidoglycan-based cell wall | murein sacculus | Staphylococcus aureus | 9274 | - |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Staphylococcus aureus | - |
methicillin resistant, gene mtgA | - |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant wild-type and mutant enzymes including gel filtration | Staphylococcus aureus |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | positive cooperativity between acceptor and donor sites of the peptidoglycan glycosyltransferase, mechanism of interaction with substrates, overview. At low concentrations the disaccharide compounds bind selectively to the acceptor site and increase the affinity of the donor site to moenomycin A by heteroallosteric activation leading to an increased MtgA binding response | Staphylococcus aureus | ? | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| MtgA | - |
Staphylococcus aureus |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7.5 | - |
assay at | Staphylococcus aureus |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | the enzyme belongs to the glycosyltransferases of family 51 (GT51), the glycosyltransferases of family 51 are essential enzymes found in bacteria with peptidoglycan cell wall. They exist in two forms: as a monofunctional domain or linked to the N-terminal end of penicillin-binding (PB) domain in bifunctional PB proteins. Both forms catalyze the polymerization of lipid II (undecaprenyl pyrophosphate-MurNAc(pentapeptide)-GlcNAc) precursor to form linear glycan chains | Staphylococcus aureus |
| malfunction | inhibition of the enzyme blocks peptidoglycan synthesis and leads to bacterial lysis and death | Staphylococcus aureus |
| additional information | the enzyme contain a conserved hydrophobic surface that mediates its interaction with the cytoplasmic membrane and renders the purified protein polydisperse. Quantitative binding study of the MtgA by surface plasmon resonance | Staphylococcus aureus |
| physiological function | the enzyme catalyze the polymerization of lipid II to form linear glycan chains, which, after cross linking by the transpeptidases, form the net-like peptidoglycan macromolecule, which encases bacteria and protects them from rupture under their high cytoplasmic pressure | Staphylococcus aureus |
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