Literature summary for 2.5.1.31 extracted from

Farha, M.A.; Czarny, T.L.; Myers, C.L.; Worrall, L.J.; French, S.; Conrady, D.G.; Wang, Y.; Oldfield, E.; Strynadka, N.C.; Brown, E.D.
Antagonism screen for inhibitors of bacterial cell wall biogenesis uncovers an inhibitor of undecaprenyl diphosphate synthase (2015), Proc. Natl. Acad. Sci. USA, 112, 11048-11053.

Cloned(Commentary)

Cloned (Comment)	Organism
gene uppS, recombinant N-terminally His-tagged enzyme expression in Escherichia coli strain BL21(DE3)	Escherichia coli

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified recombinant His-tagged enzyme in complex with inhibitor clomiphene, sitting drop vapor diffusion in the presence or absence of 1 mM clomiphene using a reservoir solution of 100 mM MES, pH 6.5, 0.16 M calcium acetate, 20% PEG 8000, 20% glycerol (+ clomiphene) or 0.1 M lithium sulfate, 0.1 M ADA 6.5, 12% w/v PEG 4000, 20% glycerol (-clomiphene), X-ray diffraction structure determination and analysis at 2.15 A resolution, molecular replacement using structure PDB ID 1X06 as a search model	Escherichia coli

Crystallization (Comment)

Organism

purified recombinant His-tagged enzyme in complex with inhibitor clomiphene, sitting drop vapor diffusion in the presence or absence of 1 mM clomiphene using a reservoir solution of 100 mM MES, pH 6.5, 0.16 M calcium acetate, 20% PEG 8000, 20% glycerol (+ clomiphene) or 0.1 M lithium sulfate, 0.1 M ADA 6.5, 12% w/v PEG 4000, 20% glycerol (-clomiphene), X-ray diffraction structure determination and analysis at 2.15 A resolution, molecular replacement using structure PDB ID 1X06 as a search model

Escherichia coli

Inhibitors

Inhibitors	Comment	Organism
clomiphene	inhibits the synthesis of undecaprenyl phosphate, antagonizes the activity of targocil	Escherichia coli
clomiphene	inhibits the synthesis of undecaprenyl phosphate, antagonizes the activity of targocil	Staphylococcus aureus
additional information	antagonistic interactions in high-throughput screening and in compound mode of action studies. MIC values and fractional inhibitory concentrations of combinations of clomiphene and antibiotics against strain CA-MRSA USA 300, overview	Escherichia coli
additional information	antagonistic interactions in high-throughput screening and in compound mode of action studies. MIC values and fractional inhibitory concentrations of combinations of clomiphene and antibiotics against strain CA-MRSA USA 300, overview	Staphylococcus aureus

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
cell wall	-	Escherichia coli	5618	-
cell wall	-	Staphylococcus aureus	5618	-

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	required	Escherichia coli
Mg2+	required	Staphylococcus aureus

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate	Escherichia coli	-	8 diphosphate + ditrans,octacis-undecaprenyl diphosphate	-	?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate	Staphylococcus aureus	-	8 diphosphate + ditrans,octacis-undecaprenyl diphosphate	-	?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate	Staphylococcus aureus USA300	-	8 diphosphate + ditrans,octacis-undecaprenyl diphosphate	-	?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate	Escherichia coli MC1061	-	8 diphosphate + ditrans,octacis-undecaprenyl diphosphate	-	?

Organism

Organism	UniProt	Comment	Textmining
Escherichia coli	P60472	gene uppsS	-
Escherichia coli MC1061	P60472	gene uppsS	-
Staphylococcus aureus	A0A0H2XGF2	gene uppsS	-
Staphylococcus aureus USA300	A0A0H2XGF2	gene uppsS	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, dialysis, and gel filtration	Escherichia coli

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate	-	Escherichia coli	8 diphosphate + ditrans,octacis-undecaprenyl diphosphate	-	?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate	-	Staphylococcus aureus	8 diphosphate + ditrans,octacis-undecaprenyl diphosphate	-	?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate	-	Staphylococcus aureus USA300	8 diphosphate + ditrans,octacis-undecaprenyl diphosphate	-	?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate	-	Escherichia coli MC1061	8 diphosphate + ditrans,octacis-undecaprenyl diphosphate	-	?

Synonyms

Synonyms	Comment	Organism
UPPs	-	Escherichia coli
UPPs	-	Staphylococcus aureus

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
37	-	assay at	Escherichia coli
37	-	assay at	Staphylococcus aureus

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.3	-	assay at	Escherichia coli
7.3	-	assay at	Staphylococcus aureus

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor	Structure
0.0075	-	pH 7.3, 37°C	Staphylococcus aureus	clomiphene

General Information

General Information	Comment	Organism
physiological function	undecaprenyl diphosphate synthase catalyzes the synthesis of a polyisoprenoid that is essential for both peptidoglycan and cell wall teichoic acid, WTA, synthesis. UppS might be an auxiliary factor involved in methicillin resistance of methicillin-resistant Staphylococcus aureus	Escherichia coli
physiological function	undecaprenyl diphosphate synthase catalyzes the synthesis of a polyisoprenoid that is essential for both peptidoglycan and cell wall teichoic acid, WTA, synthesis. UppS might be an auxiliary factor involved in methicillin resistance of methicillin-resistant Staphylococcus aureus	Staphylococcus aureus