Application | Comment | Organism |
---|---|---|
drug development | the specificity of the enzyme to eubacteria makes it a promising potential target to be exploited for antibacterial discovery to combat emerging resistance | Bacillus subtilis |
Cloned (Comment) | Organism |
---|---|
gene mraY, cloning in Escherichia coli strain DH5alpha | Bacillus subtilis |
Protein Variants | Comment | Organism |
---|---|---|
D98A | site-directed mutagenesis, the mutant shows altered pH dependence compared to the wild-type enzyme | Bacillus subtilis |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
dodecylamine | a competitive inhibitor of MraY | Bacillus subtilis | |
additional information | no inhibition by 1-diphospho-N-acetylmuramoyl-pentapeptide | Bacillus subtilis |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | the enzyme exhibits Michaelis-Menten kinetics towards the heptaprenyl phosphate and dodecaprenyl phosphate lipid substrates. The Km values for dodecaprenyl phosphate and heptaprenyl phosphate are 0.21 mM and 0.15 mM, respectively. The Km values are similar to that of the physiological lipid substrate, undecaprenyl phosphate with 0.16 mM | Bacillus subtilis |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cell wall | - |
Bacillus subtilis | 5618 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | essentially required | Bacillus subtilis |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
UDP-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala) + undecaprenyl phosphate | Bacillus subtilis | - |
UMP + Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenol | - |
r | |
UDP-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala) + undecaprenyl phosphate | Bacillus subtilis 168 | - |
UMP + Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenol | - |
r |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Bacillus subtilis | Q03521 | gene mraY | - |
Bacillus subtilis 168 | Q03521 | gene mraY | - |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
UDP-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala) + undecaprenyl phosphate = UMP + Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenol | a one-step, single displacement mechanism. The oxyanion of the polyprenyl-phosphate attacks the b-phosphate of the nucleotide substrate, leading to the formation of product lipid I and liberation of UMP. The involvement of an invariant aspartyl residue in the deprotonation of the lipid substrate is possible. Formation of a covalent reaction intermediate | Bacillus subtilis |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | the enzyme does not display any diphosphatase activity on the nucleotide substrate. No activity with UDP-GlcNAc and 1-diphospho-MurNAc-pentapeptide. Enzyme catalytic mechanism and substrate specificity, overview. The essential aspartate residue, that is invariant in the superfamily, is Asp98 in Bacillus subtilis MraY, the residue is involved in the deprotonation of the lipid substrate during the catalytic process. UDPMurNAc, UDP-MurNAc-L-Ala, UDP-MurNAc-L-Ala-D-Glu and UDPMurNAc-L-Ala-gamma-D-Glu-meso-diaminopimelate precursors of the peptidoglycan biosynthesis pathway are all substrates of the enzyme, no activity with 1-diphospho-MurNAc-pentapeptide. No activity with isopentenyl phosphate as lipid substrate, the enzyme is highly active when tested with neryl phosphate, heptaprenyl phosphate, dodecaprenyl phosphate, and pentadecaprenyl phosphate | Bacillus subtilis | ? | - |
? | |
additional information | the enzyme does not display any diphosphatase activity on the nucleotide substrate. No activity with UDP-GlcNAc and 1-diphospho-MurNAc-pentapeptide. Enzyme catalytic mechanism and substrate specificity, overview. The essential aspartate residue, that is invariant in the superfamily, is Asp98 in Bacillus subtilis MraY, the residue is involved in the deprotonation of the lipid substrate during the catalytic process. UDPMurNAc, UDP-MurNAc-L-Ala, UDP-MurNAc-L-Ala-D-Glu and UDPMurNAc-L-Ala-gamma-D-Glu-meso-diaminopimelate precursors of the peptidoglycan biosynthesis pathway are all substrates of the enzyme, no activity with 1-diphospho-MurNAc-pentapeptide. No activity with isopentenyl phosphate as lipid substrate, the enzyme is highly active when tested with neryl phosphate, heptaprenyl phosphate, dodecaprenyl phosphate, and pentadecaprenyl phosphate | Bacillus subtilis 168 | ? | - |
? | |
UDP-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala) + undecaprenyl phosphate | - |
Bacillus subtilis | UMP + Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenol | - |
r | |
UDP-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala) + undecaprenyl phosphate | the forward and reverse exchange reactions require the presence of the second substrate, undecaprenyl phosphate and UMP, respectively. No activity is detected with isopentenyl phosphate, but the enzyme is highly active with neryl phosphate, heptaprenyl phosphate, dodecaprenyl phosphate, and pentadecaprenyl phosphate | Bacillus subtilis | UMP + Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenol | - |
r | |
UDP-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala) + undecaprenyl phosphate | - |
Bacillus subtilis 168 | UMP + Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenol | - |
r | |
UDP-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala) + undecaprenyl phosphate | the forward and reverse exchange reactions require the presence of the second substrate, undecaprenyl phosphate and UMP, respectively. No activity is detected with isopentenyl phosphate, but the enzyme is highly active with neryl phosphate, heptaprenyl phosphate, dodecaprenyl phosphate, and pentadecaprenyl phosphate | Bacillus subtilis 168 | UMP + Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenol | - |
r | |
UDP-MurNAc + undecaprenyl phosphate | 24% activity compared to UDP-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala) | Bacillus subtilis | UMP + MurNAc-diphosphoundecaprenol | - |
r | |
UDP-MurNAc + undecaprenyl phosphate | 24% activity compared to UDP-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala) | Bacillus subtilis 168 | UMP + MurNAc-diphosphoundecaprenol | - |
r | |
UDP-MurNAc-(oyl-L-Ala) + undecaprenyl phosphate | 9% activity compared to UDP-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala) | Bacillus subtilis | UMP + MurNAc(oyl-L-Ala)-diphosphoundecaprenol | - |
r | |
UDP-MurNAc-(oyl-L-Ala) + undecaprenyl phosphate | 9% activity compared to UDP-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala) | Bacillus subtilis 168 | UMP + MurNAc(oyl-L-Ala)-diphosphoundecaprenol | - |
r | |
UDP-MurNAc-(oyl-L-Ala-gamma-D-Glu) + undecaprenyl phosphate | 36% activity compared to UDP-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala) | Bacillus subtilis | UMP + MurNAc(oyl-L-Ala-gamma-D-Glu)-diphosphoundecaprenol | - |
r | |
UDP-MurNAc-(oyl-L-Ala-gamma-D-Glu-meso-diaminopimelate) + undecaprenyl phosphate | 51% activity compared to UDP-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala) | Bacillus subtilis | UMP + MurNAc(oyl-L-Ala-gamma-D-Glu-meso-diaminopimelate)-diphosphoundecaprenol | - |
r |
Synonyms | Comment | Organism |
---|---|---|
MraY | - |
Bacillus subtilis |
polyprenyl-phosphate N-acetylhexosamine 1-phosphate transferase | - |
Bacillus subtilis |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Bacillus subtilis |
Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | the enzyme exhibits Michaelis-Menten kinetics towards the heptaprenyl phosphate and dodecaprenyl phosphate lipid substrates. The catalytic constants kcat are 295/min and 54/min, respectively. The kcat for heptaprenyl phosphate is by 6fold lower than those determined for the longer-chain length lipids undecaprenyl phosphate and dodecaprenyl phosphate with 340/min and 295/min, respectively | Bacillus subtilis |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.6 | - |
assay at | Bacillus subtilis |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
1 | - |
pH 7.6, 37°C | Bacillus subtilis | dodecylamine |
General Information | Comment | Organism |
---|---|---|
evolution | the enzyme is a member of the polyprenyl-phosphate N-acetylhexosamine 1-phosphate transferase, P2HPT, superfamily | Bacillus subtilis |
physiological function | enzyme MraY transferase catalyzes the first membrane step of bacterial cell wall peptidoglycan biosynthesis, namely the transfer of the N-acetylmuramoyl-pentapeptide moiety of the cytoplasmic precursor UDP- N-acetylmuramoyl-pentapeptide to the membrane transporter undecaprenyl phosphate (C55-P), yielding undecaprenyl-N-acetylmuramoyl-pentapeptide, i.e. lipid I. The MraY transferase initiates the membrane steps of peptidoglycan biosynthesis and is an essential enzyme for bacterial viability | Bacillus subtilis |