Literature summary for 2.7.8.13 extracted from

Al-Dabbagh, B.; Olatunji, S.; Crouvoisier, M.; El Ghachi, M.; Blanot, D.; Mengin-Lecreulx, D.; Bouhss, A.
Catalytic mechanism of MraY and WecA, two paralogues of the polyprenyl-phosphate N-acetylhexosamine 1-phosphate transferase superfamily (2016), Biochimie, 127, 249-257.

Search for more literature for 2.7.8.13

Application

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(Commentary)

Cloned (Comment)	Organism
gene mraY, cloning in Escherichia coli strain DH5alpha	Bacillus subtilis

Protein Variants

Protein Variants	Comment	Organism
D98A	site-directed mutagenesis, the mutant shows altered pH dependence compared to the wild-type enzyme	Bacillus subtilis

Inhibitors

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 [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

Localization	Comment	Organism	GeneOntology No.	Textmining
cell wall	-	Bacillus subtilis	5618	-

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	essentially required	Bacillus subtilis

Natural Substrates/ Products (Substrates)

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

Organism	UniProt	Comment	Textmining
Bacillus subtilis	Q03521	gene mraY	-
Bacillus subtilis 168	Q03521	gene mraY	-

Reaction

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	a

Substrates and Products (Substrate)

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

Synonyms	Comment	Organism
MraY	-	Bacillus subtilis
polyprenyl-phosphate N-acetylhexosamine 1-phosphate transferase	-	Bacillus subtilis

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
37	-	assay at	Bacillus subtilis

Turnover Number [1/s]

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

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.6	-	assay at	Bacillus subtilis

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor	Structure
1	-	pH 7.6, 37°C	Bacillus subtilis	dodecylamine

General Information

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

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Release 2023.1 (January 2023)