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Information on EC 2.5.1.31 - ditrans,polycis-undecaprenyl-diphosphate synthase [(2E,6E)-farnesyl-diphosphate specific] and Organism(s) Escherichia coli and UniProt Accession P60472
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2.5.1.31 ditrans,polycis-undecaprenyl-diphosphate synthase [(2E,6E)-farnesyl-diphosphate specific]IUBMB Comments
Undecaprenyl pyrophosphate synthase catalyses the consecutive condensation reactions of a farnesyl diphosphate with eight isopentenyl diphosphates, in which new cis-double bonds are formed, to generate undecaprenyl diphosphate that serves as a lipid carrier for peptidoglycan synthesis of bacterial cell wall .
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Word Map
- 2.5.1.31
-
isoprenoids
- cis-prenyltransferase
- prenyltransferases
- dolichols
- luteus
- dhdds
- trans-prenyltransferases
- pharmacology
-
octaprenyl
- drug development
- medicine
The taxonomic range for the selected organisms is: Escherichia coli
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
Reaction Schemes
Synonyms
undecaprenyl diphosphate synthase, undecaprenyl pyrophosphate synthase, dehydrodolichyl diphosphate synthase, upp synthase, ddpps, undecaprenyl pyrophosphate synthetase, upp synthetase, z-prenyl diphosphate synthase, undecaprenyl-diphosphate synthase, isosesquilavandulyl diphosphate synthase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
UPPs
-
bactoprenyl-diphosphate synthase
-
-
-
-
C55-OO synthetase
-
-
-
-
C55PP synthetase
-
-
-
-
cis,polyprenyl diphosphate synthase
-
-
-
-
CPDS
-
-
-
-
DDPPs
-
-
-
-
dehydrodolichyl diphosphate synthase
-
-
-
-
di-trans,poly-cis-undecaprenyl-diphosphate synthase
-
-
-
-
synthetase, undecaprenyl pyrophosphate
-
-
-
-
undecaprenyl diphosphate synthase
undecaprenyl diphosphate synthetase
-
-
-
-
undecaprenyl pyrophosphate synthase
-
-
undecaprenyl pyrophosphate synthetase
undecaprenyl-diphosphate synthase
-
-
-
-
UPP synthetase
UPPs
-
-
UPS
-
-
-
-
Z-prenyl diphosphate synthase
-
-
-
-
additional information
undecaprenyl diphosphate synthase
-
-
-
-
undecaprenyl pyrophosphate synthetase
-
-
-
-
UPP synthetase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate = 8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
active site structure, detailed catalytic mechanism, substrate binding mechanism, D26, H43, S71, N74, and R77 are involved
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate = 8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate = 8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
active site structure and catalytic mechanism
-
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate = 8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
active site structure, detailed catalytic mechanism, substrate binding mechanism, D26, H43, S71, N74, and R77 are involved
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate = 8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
substrate binding mode and catalytic mechanism involving active site residue Asp26 which serves as general base, overview
-
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate = 8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
catalytic mechanism, overview
-
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate = 8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
ditrans,octacis-undecaprenyl diphosphate substrate binding mode and catalytic mechanism involving active site residue Asp26 which serves as general base, overview
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
alkenyl group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
-
-
SYSTEMATIC NAME
IUBMB Comments
(2E,6E)-farnesyl-diphosphate:isopentenyl-diphosphate cistransferase (adding 8 isopentenyl units)
Undecaprenyl pyrophosphate synthase catalyses the consecutive condensation reactions of a farnesyl diphosphate with eight isopentenyl diphosphates, in which new cis-double bonds are formed, to generate undecaprenyl diphosphate that serves as a lipid carrier for peptidoglycan synthesis of bacterial cell wall [3].
CAS REGISTRY NUMBER
COMMENTARY
52350-87-5
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
2-nitrileanilinogeranyl diphosphate + 9 isopentenyl diphosphate
9 diphosphate + 2-nitrileanilinobactoprenyl diphosphate
the fluorescent substrate analogue undergoes a 2.5fold increase in fluorescence upon isoprenoid chain elongation, and this increase in fluorescence can be utilized to monitor the activity and inhibition of UPPS in 96-well plate assays
-
-
?
(2E,6E)-8-(N-methyl-2-aminobenzoyloxy)-3,7-dimethyl-2,6-octandien-1-diphosphate + 8 isopentenyl diphosphate
?
-
a fluorescent analog of farnesyl diphosphate
-
-
?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate
diphosphate + di-trans,poly-cis-undecaprenyl diphosphate
-
-
-
?
(2E,6E)-farnesyl thiodiphosphate + isopentenyl diphosphate
?
-
weak activity, 10000000fold lower than with (2E,6E)-farnesyl diphosphate
-
-
?
7-(2,6-dimethyl-8-diphospho-2,6-octadienyloxy)-8-methyl-4-trifluoromethyl-chromen-2-one geranyl diphosphate + isopentenyl diphosphate
?
-
fluorescent analogue of (2E,6E)-farnesyl diphosphate, alternative substrate and inhibitor
-
-
?
di-trans-poly-cis-decaprenyl diphosphate + isopentenyl diphosphate
diphosphate + di-trans-poly-cis-undecaprenyl diphosphate
farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + undecaprenyl diphosphate
-
neither dimethylallyl diphosphate nor geranyl diphosphate act as priming substrate for the enzyme
-
-
?
farnesyl diphosphate + isopentenyl diphosphate
diphosphate + di-trans-poly-cis-undecaprenyl diphosphate
farnesyl phosphate + isopentenyl diphosphate
phosphate + di-trans-poly-cis-undecaprenyl diphosphate
-
low activity
-
-
?
geranyl diphosphate + isopentenyl diphosphate
?
-
C10 GPP displays a 90fold larger Km value compared with (2E,6E)-farnesyl diphosphate
-
-
?
geranyl diphosphate + isopentenyl diphosphate
diphosphate + ?
-
less effective than farnesyl diphosphate
-
-
?
geranylgeranyl diphosphate + isopentenyl diphosphate
?
-
containing a larger C20 hydrocarbon tail, is an equally good substrate
-
-
?
geranylgeranyl diphosphate + isopentenyl diphosphate
diphosphate + ?
-
as effective as farnesyl diphosphate
-
-
?
isopentenyl diphosphate + (E,E)-(2-diazo-3-trifluoropropionyloxy)geranyl diphosphate
(E,E)-(2-diazo-3-trifluoropropionyloxy)polyprenyl diphosphate + diphosphate
-
-
-
-
?
isopentenyl diphosphate + farnesyl diphosphate
C55-polyprenyl diphosphate + C50-polyprenyl diphosphate + diphosphate
isopentenyl diphosphate + geranylgeranyl diphosphate
C55-polyprenyl diphosphate + C50-polyprenyl diphosphate + diphosphate
-
-
-
-
?
isopentenyl diphosphate + S-farnesyl thiodiphosphate
?
-
weak activity, 10000000fold lower than with farnesyl diphosphate
-
-
?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
-
-
-
?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
-
-
-
?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
-
-
-
?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
-
-
-
-
?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
-
-
-
?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
-
-
-
?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
-
-
-
-
?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
-
-
-
?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
the enzyme is responsible for the biogenesis of undecaprenyl phosphate, an indispensable glycosyl carrier lipid in bacterial cell wall biosynthesis
-
-
?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
the enzyme catalyzes the synthesis of the C55 lipid undecaprenyl diphosphate through eight consecutive condensations of isopentenyl pyrophosphate
-
-
?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
-
-
-
-
?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
-
-
-
?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
-
-
quantification of product distribution of UPPs catalyzed coupling of (2E,6E)-farnesyl diphosphate and isopentenyl diphosphate under various reaction conditions
-
?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
-
catalyzes the condensation of eight molecules of isopentenyl pyrophosphate (IPP) with farnesyl diphosphate (FPP) to generate C55 undecaprenyl diphosphate. With a variety of different ratios of enzyme to substrate and FPP to IPP in the presence or absence of Triton, different product distributions are found
-
-
?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
-
UPPS catalyzes eight consecutive condensation steps of IPP with FPP to form C55 final product
-
-
?
di-trans-poly-cis-decaprenyl diphosphate + isopentenyl diphosphate
diphosphate + di-trans-poly-cis-undecaprenyl diphosphate
-
di-trans-poly-cis-decaprenyl diphosphate is farnesyl diphosphate
-
-
?
di-trans-poly-cis-decaprenyl diphosphate + isopentenyl diphosphate
diphosphate + di-trans-poly-cis-undecaprenyl diphosphate
-
di-trans-poly-cis-decaprenyl diphosphate is farnesyl diphosphate, the diphosphate head group of farnesyl diphosphate is bound to the backbone of NHs pf G29 and R30 as well as the side chains of N28, R30, and R39 through hydrogen bonds, H43 may stabilize the farnesyl cation intermediate during catalysis being near to the C2 carbon of farnesyl diphosphate
-
-
?
farnesyl diphosphate + isopentenyl diphosphate
diphosphate + di-trans-poly-cis-undecaprenyl diphosphate
-
consecutive condensation of 8 molecules of isopentenyl diphosphate with farnesyl diphosphate to form the lipid carrier undecaprenyl diphosphate to mediate bacterial peptidoglycan synthesis
-
-
?
farnesyl diphosphate + isopentenyl diphosphate
diphosphate + di-trans-poly-cis-undecaprenyl diphosphate
consecutive condensation of 8 molecules of isopentenyl diphosphate with farnesyl diphosphate to form the lipid carrier undecaprenyl diphosphate to mediate bacterial peptidoglycan synthesis
-
-
?
farnesyl diphosphate + isopentenyl diphosphate
diphosphate + di-trans-poly-cis-undecaprenyl diphosphate
-
consecutive condensation of 8 molecules of isopentenyl diphosphate with farnesyl diphosphate to form the lipid carrier undecaprenyl diphosphate to mediate bacterial peptidoglycan synthesis, the final product has C55 chain length
-
-
?
farnesyl diphosphate + isopentenyl diphosphate
diphosphate + di-trans-poly-cis-undecaprenyl diphosphate
-
consecutive condensation of 8 molecules of isopentenyl diphosphate with farnesyl diphosphate to form the lipid carrier undecaprenyl diphosphate to mediate bacterial peptidoglycan synthesis, the final product has C55-C60 chain length, molecular 3D-structural modeling of the reaction product
-
-
?
farnesyl diphosphate + isopentenyl diphosphate
diphosphate + di-trans-poly-cis-undecaprenyl diphosphate
stereochemistry of the reaction
-
-
?
farnesyl diphosphate + isopentenyl diphosphate
diphosphate + di-trans-poly-cis-undecaprenyl diphosphate
-
the phosphate head group of farnesyl diphosphate is bound to the positively charged Arg residues and the hydrocarbon moiety interacts with hydrophobic amino acids including L85, L88, and F89, located on the alpha3-helix of the enzyme
-
-
?
isopentenyl diphosphate + farnesyl diphosphate
C55-polyprenyl diphosphate + C50-polyprenyl diphosphate + diphosphate
-
-
-
?
isopentenyl diphosphate + farnesyl diphosphate
C55-polyprenyl diphosphate + C50-polyprenyl diphosphate + diphosphate
-
-
-
-
?
isopentenyl diphosphate + farnesyl diphosphate
C55-polyprenyl diphosphate + C50-polyprenyl diphosphate + diphosphate
-
the major product of the wild-type enzyme, and mutant enzymes H103A, V103A, V105A and I62A in presence of Triton is C55-polyprenyl diphosphate. Mutant enzyme L137A produces C55-polyprenyl diphosphate, C60-polyprenyl diphosphate and C65-polyprenyl diphosphate in the ration 55:41:4
?
isopentenyl diphosphate + farnesyl diphosphate
C55-polyprenyl diphosphate + C50-polyprenyl diphosphate + diphosphate
-
-
product distribution under various reaction conditions. In the presence of excess farnesyl diphosphate the intermediates C25-C50 accumulate
?
isopentenyl diphosphate + farnesyl diphosphate
C55-polyprenyl diphosphate + C50-polyprenyl diphosphate + diphosphate
-
-
with 0.02% Triton X-100 the main product is the C55-compound, C50-compound is the minor product. With 0.1% Triton X-100 the C50-polyprenyl diphosphate is the main product, the C55-polyprenyl diphosphate and the C45-polyprenyl diphosphate are minor products. With 0.5% Triton X-100 the C50-polyprenyl diphosphate compound and the C45-compound are the main products, the C55-compound is not formed
?
isopentenyl diphosphate + farnesyl diphosphate
C55-polyprenyl diphosphate + C50-polyprenyl diphosphate + diphosphate
-
trans,trans-farnesyl diphosphate
-
-
?
additional information
?
-
-
catalyzes the consecutive condensation reactions of a farnesyl diphosphate (FPP) with eight isopentenyl diphosphates (IPP), in which new cis-double bonds are formed, to generate undecaprenyl diphosphate that serves as a lipid carrier for peptidoglycan synthesis of bacterial cell wall
-
-
?
additional information
?
-
catalyzes the consecutive condensation reactions of a farnesyl diphosphate (FPP) with eight isopentenyl diphosphates (IPP), in which new cis-double bonds are formed, to generate undecaprenyl diphosphate that serves as a lipid carrier for peptidoglycan synthesis of bacterial cell wall
-
-
?
additional information
?
-
development of assay methods for UPPS, the difference in substrate utilization between forms of UPPS from different species has major implications for UPPS inhibitor development, assay construction, and the development of polysaccharide biosynthesis probes. 2-Nitrileanilinogeranyl diphosphate (2CNA-GPP) is a general and effective continuous probe for UPPS activity. No activity with 2-amideanilinogeranyl diphosphate due to competition with diphosphate
-
-
?
additional information
?
-
-
development of assay methods for UPPS, the difference in substrate utilization between forms of UPPS from different species has major implications for UPPS inhibitor development, assay construction, and the development of polysaccharide biosynthesis probes. 2-Nitrileanilinogeranyl diphosphate (2CNA-GPP) is a general and effective continuous probe for UPPS activity. No activity with 2-amideanilinogeranyl diphosphate due to competition with diphosphate
-
-
?
additional information
?
-
-
role of the hydrocarbon moiety of the allylic substrate in the reaction
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
farnesyl diphosphate + isopentenyl diphosphate
diphosphate + di-trans-poly-cis-undecaprenyl diphosphate
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
-
-
-
?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
-
-
-
?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
-
-
-
-
?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
the enzyme is responsible for the biogenesis of undecaprenyl phosphate, an indispensable glycosyl carrier lipid in bacterial cell wall biosynthesis
-
-
?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
-
-
-
-
?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
-
-
-
?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
-
catalyzes the condensation of eight molecules of isopentenyl pyrophosphate (IPP) with farnesyl diphosphate (FPP) to generate C55 undecaprenyl diphosphate. With a variety of different ratios of enzyme to substrate and FPP to IPP in the presence or absence of Triton, different product distributions are found
-
-
?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
-
UPPS catalyzes eight consecutive condensation steps of IPP with FPP to form C55 final product
-
-
?
farnesyl diphosphate + isopentenyl diphosphate
diphosphate + di-trans-poly-cis-undecaprenyl diphosphate
-
consecutive condensation of 8 molecules of isopentenyl diphosphate with farnesyl diphosphate to form the lipid carrier undecaprenyl diphosphate to mediate bacterial peptidoglycan synthesis
-
-
?
farnesyl diphosphate + isopentenyl diphosphate
diphosphate + di-trans-poly-cis-undecaprenyl diphosphate
consecutive condensation of 8 molecules of isopentenyl diphosphate with farnesyl diphosphate to form the lipid carrier undecaprenyl diphosphate to mediate bacterial peptidoglycan synthesis
-
-
?
farnesyl diphosphate + isopentenyl diphosphate
diphosphate + di-trans-poly-cis-undecaprenyl diphosphate
-
consecutive condensation of 8 molecules of isopentenyl diphosphate with farnesyl diphosphate to form the lipid carrier undecaprenyl diphosphate to mediate bacterial peptidoglycan synthesis, the final product has C55 chain length
-
-
?
farnesyl diphosphate + isopentenyl diphosphate
diphosphate + di-trans-poly-cis-undecaprenyl diphosphate
-
consecutive condensation of 8 molecules of isopentenyl diphosphate with farnesyl diphosphate to form the lipid carrier undecaprenyl diphosphate to mediate bacterial peptidoglycan synthesis, the final product has C55-C60 chain length, molecular 3D-structural modeling of the reaction product
-
-
?
additional information
?
-
-
catalyzes the consecutive condensation reactions of a farnesyl diphosphate (FPP) with eight isopentenyl diphosphates (IPP), in which new cis-double bonds are formed, to generate undecaprenyl diphosphate that serves as a lipid carrier for peptidoglycan synthesis of bacterial cell wall
-
-
?
additional information
?
-
catalyzes the consecutive condensation reactions of a farnesyl diphosphate (FPP) with eight isopentenyl diphosphates (IPP), in which new cis-double bonds are formed, to generate undecaprenyl diphosphate that serves as a lipid carrier for peptidoglycan synthesis of bacterial cell wall
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mg2+
Mn2+
sulfate
-
2 molecules bound per enzyme dimer, 1 at each active site, binding structure
Triton
-
3 Triton (T1, T2, and T3) are located in the two monomers with one on the top portion of the active site tunnel in monomer A and the other two occupying the overall tunnel of monomer B
Mg2+
role of the metal ion in catalysis, required for binding of isopentenyl diphosphate to the enzyme, best at 1 mM, low activity at 50 mM, Asp26 is required for efficient binding, Mg2+ is bound to the diphosphate of farnesyl diphosphate in the wild-type enzyme, but to the diphosphate of isopentenyl diphosphate in the mutant D26A, Mg2+ is not required for the overall structure stability, overview
Mg2+
-
required, best at 0.5 mM MgCl2, 2 Mg2+ are bound at the subunit interface, binding structure
Mg2+
-
required, enzyme utilizes a Asp-rich motif for substrate binding via Mg2+
Mg2+
role of the metal ion in catalysis, required for binding of isopentenyl diphosphate to the enzyme, best at 1 mM, low activity at 50 mM, Asp26 is required for efficient binding, Mg2+ is bound to the diphosphate of farnesyl diphosphate in the wild-type enzyme, but to the diphosphate of isopentenyl diphosphate in the mutant D26A, Mg2+ is not required for the overall structure stability, overview
Mg2+
-
is chelated by His199 and Glu213 from different subunits and possibly plays astructural rather than catalytic role
Mg2+
-
required, structures of Mg2+ binding of wild-type and mutant UPPS, overview
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(1-hydroxy-2-[3'-[(naphthalene-2-sulfonyl)amino][1,1'-biphenyl]-3-yl]ethane-1,1-diyl)bis(phosphonic acid)
-
(2S,3R,4S,5S,6R)-2-(3-((4-((3-(4,5-dihydro-1H-imidazol-2-yl)-phenyl)ethynyl)phenyl)ethynyl)phenoxy)-6-(hydroxymethyl)-tetrahydro-2H-pyran-3,4,5-triol
-
(2Z)-2-hydroxy-4-oxo-4-[[3-(3-phenoxyphenyl)propyl]amino]but-2-enoic acid
-
(2Z)-2-hydroxy-4-[3-[3-(octyloxy)phenoxy]phenyl]-4-oxobut-2-enoic acid
-
(2Z)-4-([3-[3-(hexyloxy)phenyl]propyl]amino)-2-hydroxy-4-oxobut-2-enoic acid
-
(2Z)-4-[3-[3-(decyloxy)phenoxy]phenyl]-2-hydroxy-4-oxobut-2-enoic acid
-
(2Z)-4-[[3-([1,1'-biphenyl]-3-yl)propyl]amino]-2-hydroxy-4-oxobut-2-enoic acid
-
1,4-bis(6-(1,4,5,6-tetrahydropyrimidin-2-yl)-1H-indol-2-yl)-benzene
-
1-[[3-(hexyloxy)phenyl]methyl]-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid
-
2,2'-(5,5'-(1,3-phenylenebis(ethyne-2,1-diyl))bis(3-bromo-5,1-phenylene))diethanamine
-
2,2'-(E)-ethene-1,2-diylbis[6-(4,5-dihydro-1H-imidazol-2-yl)-1H-indole]
-
2-(2-[[5-(1-benzofuran-2-yl)-4-phenyl-4H-1,2,4-triazol-3-yl]sulfanyl]acetamido)benzoic acid
-
2-[4-[(E)-2-chloro-1,2-diphenylethenyl]phenoxy]-N,N-diethylethan-1-amine
-
2-[[(2E)-2-cyano-3-[1-[(naphthalen-1-yl)methyl]-1H-indol-3-yl]prop-2-enoyl]amino]benzoic acid
-
2-[[(2E)-2-cyano-3-[3-[(4-fluorophenyl)methoxy]phenyl]prop-2-enoyl]amino]benzoic acid
-
3-(2-chlorophenyl)-5-methyl-N-[4-(propan-2-yl)phenyl]-1,2-oxazole-4-carboxamide
-
3-(4-chlorophenyl)-N'-[(2,4-dihydroxyphenyl)methyl]-1H-pyrazole-5-carbohydrazide
-
3-([1,1'-biphenyl]-3-yl)-1-(2-hydroxy-2,2-diphosphonoethyl)pyridin-1-ium
-
3-[(2E)-3,7-dimethylocta-2,6-dien-1-yl]-1-(2,2-diphosphonoethyl)pyridin-1-ium
-
3-[(5Z)-5-[[5-(2,4-dichlorophenyl)furan-2-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]propanoic acid
-
3-[5-(5,6-dihydrobenzimidazo[1,2-c]quinazolin-6-yl)-2,5-dihydrofuran-2-yl]benzenesulfonamide
barely inhibits UPPS of Escherichia coli
4-(dibenzo[b,d]furan-4-yl)-1-(2-hydroxy-2,2-diphosphonoethyl)pyridin-1-ium
-
4-[3-[([1,1'-biphenyl]-4-carbonyl)amino]phenoxy]benzene-1,2-dicarboxylic acid
-
5-([5-[(1H-benzimidazol-2-yl)sulfanyl]furan-2-yl]methylidene)-1,3-diazinane-2,4,6-trione
-
5-benzyl-3-[1-(4-cyclohexylanilino)ethenyl]-4-hydroxy-5,6-dihydropyridin-2(1H)-one
-
5-benzyl-4-hydroxy-3-[1-[4-(1H-imidazol-1-yl)anilino]ethenyl]-5,6-dihydropyridin-2(1H)-one
-
5-benzyl-N-(4-cyclohexylphenyl)-4-hydroxy-2-oxo-2,5-dihydro-1H-pyrrole-3-carboxamide
-
5-benzyl-N-[4-(hexyloxy)phenyl]-4-hydroxy-2-oxo-2,5-dihydro-1H-pyrrole-3-carboxamide
-
5-bromo-2-[4-(6-chloro-2,3-dihydro-1H-indole-1-sulfonyl)benzamido]benzoic acid
-
6-benzyl-4-hydroxy-3-[1-[4-(1H-imidazol-1-yl)anilino]ethenyl]-5,6-dihydropyridin-2(1H)-one
-
clomiphene
inhibits the synthesis of undecaprenyl phosphate, antagonizes the activity of targocil
MAC-0547630
the inhibitor shows great promise as a whole cell-active probe due to its selective and potent inhibition of undecaprenyl diphosphate synthase
N-(3,5-dichlorophenyl)-4-hydroxy-2-oxo-5-phenyl-2,5-dihydro-1H-pyrrole-3-carboxamide
-
N-(4-chlorophenyl)-4-hydroxy-2-oxo-5-phenyl-2,5-dihydro-1H-pyrrole-3-carboxamide
-
N-(4-cyclohexylphenyl)-4-hydroxy-2-oxo-2,5-dihydro-1H-pyrrole-3-carboxamide
-
N-(4-cyclohexylphenyl)-4-hydroxy-2-oxo-5-(2-phenylethyl)-2,5-dihydro-1H-pyrrole-3-carboxamide
-
N-(4-cyclohexylphenyl)-4-hydroxy-2-oxo-5-phenyl-2,5-dihydro-1H-pyrrole-3-carboxamide
-
N-([1,1'-biphenyl]-4-yl)-4-hydroxy-2-oxo-5-(2-phenylethyl)-2,5-dihydro-1H-pyrrole-3-carboxamide
-
N-[2-[(2-[1-[(3-amino-3-iminopropyl)amino]ethenyl]-1-methyl-1H-imidazol-4-yl)acetyl]-1-methyl-1H-imidazol-4-yl]-N2-(diaminomethylidene)glycinamide
weak inhibition
N-[3-(4,5-dihydro-1H-imidazol-2-yl)phenyl]-N'-(3-phenoxyphenyl)biphenyl-4,4'-dicarboxamide
-
N-[3-[3,4-di(prop-1-en-2-yl)phenoxy]phenyl][1,1'-biphenyl]-4-carboxamide
-
N1,N4-bis(4-(4,5-dihydro-1H-imidazol-2-yl)phenyl)-2-nitroterephthalamide
-
N1,N4-bis(4-(4,5-dihydro-1H-imidazol-2-yl)phenyl)-2-nitroterephthalamide dihydrochloride
-
N1,N4-bis[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]-2-nitrobenzene-1,4-dicarboxamide
-
N4,N4'-bis(3-(1,4,5,6-tetrahydropyrimidin-2-yl)phenyl)biphenyl-4,4'-dicarboxamide
-
N4,N4'-bis(3-(4,5-dihydro-1H-imidazol-2-yl)phenyl)-[1,1'-biphenyl]-4,4'-bicarboxamide
i.e. BPH-1358
N4,N4'-bis(3-(4,5-dihydro-1H-imidazol-2-yl)phenyl)biphenyl-4,4'-bis(carbothioamide)
-
N4-(3-(4,5-dihydro-1H-imidazol-2-yl)phenyl)-N4'-(3-(hexyloxy)-phenyl)-[1,1-biphenyl]-4,4-dicarboxamide
-
N4-(3-(4,5-dihydro-1H-imidazol-2-yl)phenyl)-N4'-(3-methoxyphenyl)-[1,1-biphenyl]-4,4-dicarboxamide
-
N4-(3-(4,5-dihydro-1H-imidazol-2-yl)phenyl)-N4'-3(-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)phenyl)-[1,1-biphenyl]-4,4-dicarboxamide
-
[(5Z)-5-[[5-(4-chloro-2-methylphenyl)furan-2-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid
-
[1-hydroxy-2-(3-[3-[3-(2-hydroxy-2,2-bis-phosphono-ethyl)-biphenyl-3-ylsulfamoyl]-benzenesulfonylamino]-biphenyl-3-yl)-1-phosphono-ethyl]-phosphonic acid
-
[1-hydroxy-2-([1(1),2(1):2(3),3(1)-terphenyl]-1(3)-yl)ethane-1,1-diyl]bis(phosphonic acid)
-
[1-hydroxy-2-([1(1),2(1):2(3),3(1)-terphenyl]-1(4)-yl)ethane-1,1-diyl]bis(phosphonic acid)
-
-
[1-hydroxy-2-([1(1),2(1):2(4),3(1)-terphenyl]-1(3)-yl)ethane-1,1-diyl]bis(phosphonic acid)
-
[1-hydroxy-2-[([1(1),2(1):2(3),3(1)-terphenyl]-1(3)-yl)oxy]ethane-1,1-diyl]bis(phosphonic acid)
-
[1-hydroxy-3-([1(1),2(1):2(2),3(1)-terphenyl]-1(3)-yl)propane-1,1-diyl]bis(phosphonic acid)
-
[1-hydroxy-3-([1(1),2(1):2(3),3(1)-terphenyl]-1(3)-yl)propane-1,1-diyl]bis(phosphonic acid)
-
[1-hydroxy-3-([1(1),2(1):2(4),3(1)-terphenyl]-1(3)-yl)propane-1,1-diyl]bis(phosphonic acid)
-
[2-([1,1'-biphenyl]-3-yl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
-
[2-[3-(dibenzo[b,d]furan-4-yl)phenyl]-1-hydroxy-1,1-ethanediyl]bis(phosphonic acid)
i.e. BPH-629. A pharmacophore model is designed on a known bisphosphonate BPH-629 and used to prepare an enriched compound library that was further docked into UppS conformational ensemble generated by molecular dynamics experiment. The docking results in three anthranilic acid derivatives with promising inhibitory activity against the enzyme
[2-[3-(dibenzo[b,d]furan-4-yl)phenyl]-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
-
[3-(3,4-dichlorophenyl)-4,5-dihydro-1,2-oxazole-5,5-diyl]bis(phosphonic acid)
-
[3-[4-(dibenzo[b,d]furan-4-yl)phenyl]-1-hydroxypropane-1,1-diyl]bis(phosphonic acid)
-
[hydroxy([1(1),2(1):2(3),3(1)-terphenyl]-1(3)-yl)methylene]bis(phosphonic acid)
-
[[(9-ethyl-9H-carbazol-3-yl)amino](hydroxy)methylene]bis(phosphonic acid)
-
3-[5-(5,6-dihydrobenzimidazo[1,2-c]quinazolin-6-yl)-2,5-dihydrofuran-2-yl]benzenesulfonamide
7-(2,6-dimethyl-8-diphospho-2,6-octadienyloxy)-8-methyl-4-trifluoromethyl-chromen-2-one geranyl diphosphate
-
competitive inhibitor, substrate analogue prepared and utilized to study ligand interactions
Triton X-100
-
C55 is retained in the active site for further elongation, whereas the kcat is increased by 190fold under steady-state condition by 0.1% Triton X-100
3-[5-(5,6-dihydrobenzimidazo[1,2-c]quinazolin-6-yl)-2,5-dihydrofuran-2-yl]benzenesulfonamide
i.e. HTS04781. contrary to Helicobacter pylori, HTS04781 is almost not inhibitory in Escherichia coli
3-[5-(5,6-dihydrobenzimidazo[1,2-c]quinazolin-6-yl)-2,5-dihydrofuran-2-yl]benzenesulfonamide
barely inhibits UPPS of Escherichia coli
N,N'-bis(6-chloro-1,3-benzothiazol-2-yl)methanedisulfonamide
i.e. BTB06061
N,N'-bis(6-chloro-1,3-benzothiazol-2-yl)methanedisulfonamide
barely inhibits UPPS of 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
-
additional information
screening of inhibitory activities of a series of amidine and bisamidine compounds against Staphylococcus aureus and Escherichia coli, overview
-
additional information
-
screening of inhibitory activities of a series of amidine and bisamidine compounds against Staphylococcus aureus and Escherichia coli, overview
-
additional information
-
farnesol (1 mM) lacking the diphosphate does not inhibit the UPPS reaction
-
additional information
-
a small-molecule screening platform for the discovery of inhibitors of undecaprenyl diphosphate synthase
-
additional information
a small-molecule screening platform for the discovery of inhibitors of undecaprenyl diphosphate synthase
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Triton
-
0.01 microM of UPPs with 5 microM of (2E,6E)-farnesyl diphosphate and 50 microM of isopentenyl diphosphate, 0.5 mM MgCl2, and 50 mM KCl in Hepes buffer (pH 7.5) is 190fold less active (0.013 s-1) for the IPP consumption in the absence of Triton
Triton
-
the UPPs steady-state kcat value in the presence of 0.1% Triton is 190fold larger than in the absence of Triton
Triton X-100
-
1.5% v/v, 2 molecules are bound in the active site tunnel of the beta-subunit, binding structure
Triton X-100
-
no activity in the activation by Triton X-100 is almost saturated at a concentration of 0.02%
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0011 - 0.0015
(2E,6E)-8-(N-methyl-2-aminobenzoyloxy)-3,7-dimethyl-2,6-octandien-1-diphosphate
-
pH 7.5, 25°C
0.00069
7-(2,6-dimethyl-8-diphospho-2,6-octadienyloxy)-8-methyl-4-trifluoromethyl-chromen-2-one geranyl diphosphate
-
alternative substrate, pH 7.5, 25°C
0.00037
(2E,6E)-farnesyl diphosphate
pH 7.5, 25°C, wild type with 1 mM MgCl2
0.00044
(2E,6E)-farnesyl diphosphate
pH 7.5, 25°C, wild type with 3 mM MgCl2
0.00046
(2E,6E)-farnesyl diphosphate
pH 7.5, 25°C, D26K mutant with 0.5 mM MgCl2
0.00055
(2E,6E)-farnesyl diphosphate
pH 7.5, 25°C, D26R mutant with 0.5 mM MgCl2
0.00067
(2E,6E)-farnesyl diphosphate
pH 7.5, 25°C, D26E mutant with 0.5 mM MgCl2
0.0015
(2E,6E)-farnesyl diphosphate
pH 7.5, 25°C, wild type with 0.05 mM MgCl2
0.00157
(2E,6E)-farnesyl diphosphate
pH 7.5, 25°C, wild type with 50 mM MgCl2
0.0092
isopentenyl diphosphate
pH 7.5, 25°C, D26K mutant with 0.5 mM MgCl2
0.0097
isopentenyl diphosphate
pH 7.5, 25°C, wild type with 1 mM MgCl2
0.0115
isopentenyl diphosphate
pH 7.5, 25°C, wild type with 0.05 mM MgCl2
0.0175
isopentenyl diphosphate
pH 7.5, 25°C, wild type with 3 mM MgCl2
0.0208
isopentenyl diphosphate
pH 7.5, 25°C, D26E mutant with 0.5 mM MgCl2
0.0223
isopentenyl diphosphate
pH 7.5, 25°C, D26R mutant with 0.5 mM MgCl2
0.291
isopentenyl diphosphate
pH 7.5, 25°C, wild type with 50 mM MgCl2
0.0004
(2E,6E)-farnesyl diphosphate
-
mutant enzyme W91F, pH 7.5, 25°C, wild-type enzyme, pH 7.5, 25°C
0.0004
(2E,6E)-farnesyl diphosphate
-
mutant enzymes E73A, D150A and D218A, pH 7.5, 25°C; wild-type enzyme, pH 7.5, 25°C
0.0004
farnesyl diphosphate
-
mutant enzymes E73A, D150A and D218A, pH 7.5, 25°C
0.0004
farnesyl diphosphate
mutant enzyme E73A, N74A and E81A, pH 7.5, 25°C
0.0041
isopentenyl diphosphate
-
pH 7.5, 25°C, wild-type enzyme, with farnesyl diphosphate
0.0041
isopentenyl diphosphate
-
wild type, with (2E,6E)-farnesyl diphosphate, 25°C, pH 7.5
0.013
isopentenyl diphosphate
-
pH 7.5, 25°C, wild-type enzyme, with geranylgeranyl diphosphate
0.013
isopentenyl diphosphate
-
wild type, with geranylgeranyl diphosphate, 25°C, pH 7.5
0.018
isopentenyl diphosphate
-
pH 7.5, 25°C, mutant F89A, with geranylgeranyl diphosphate
0.018
isopentenyl diphosphate
-
F89A mutant, with geranylgeranyl diphosphate, 25°C, pH 7.5
0.042
isopentenyl diphosphate
-
pH 7.5, 25°C, mutant L88A, with geranylgeranyl diphosphate
0.042
isopentenyl diphosphate
-
L88A mutant, with geranylgeranyl diphosphate, 25°C, pH 7.5
0.06
isopentenyl diphosphate
-
pH 7.5, 25°C, mutant L85A, with geranylgeranyl diphosphate
0.06
isopentenyl diphosphate
-
L85A mutant, with geranylgeranyl diphosphate, 25°C, pH 7.5
0.084
isopentenyl diphosphate
-
pH 7.5, 25°C, mutant F89A, with farnesyl diphosphate
0.084
isopentenyl diphosphate
-
F89A mutant, with (2E,6E)-farnesyl diphosphate, 25°C, pH 7.5
0.173
isopentenyl diphosphate
-
pH 7.5, 25°C, mutant L88A, with farnesyl diphosphate
0.173
isopentenyl diphosphate
-
L88A mutant, with (2E,6E)-farnesyl diphosphate, 25°C, pH 7.5
0.279
isopentenyl diphosphate
-
pH 7.5, 25°C, recombinant mutant H199A/E213A
0.617
isopentenyl diphosphate
-
pH 7.5, 25°C, mutant L85A, with farnesyl diphosphate
0.617
isopentenyl diphosphate
-
L85A mutant, with (2E,6E)-farnesyl diphosphate, 25°C, pH 7.5
additional information
additional information
-
steady-state kinetics, single turnover measurements with substrate geranylgeranyl diphosphate
-
additional information
additional information
-
fluorescence-based UPPS kinetic measurements, kinetics of the single-turnover reaction of (2E,6E)-8-O-(N-methyl-2-aminobenzoyl)-3,7-dimethyl-2,6-octandien-1-diphosphate chain elongation catalyzed by UPPS, overview
-
additional information
additional information
-
pre-steady-state UPPS kinetics, single-turnover, kinetic analysis, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
11.2
(2E,6E)-8-(N-methyl-2-aminobenzoyloxy)-3,7-dimethyl-2,6-octandien-1-diphosphate
-
pH 7.5, 25°C
0.00000031
(2E,6E)-farnesyl thiodiphosphate
-
much smaller than using (2E,6E)-farnesyl diphosphate, pH 7.5, 25°C
0.02
7-(2,6-dimethyl-8-diphospho-2,6-octadienyloxy)-8-methyl-4-trifluoromethyl-chromen-2-one geranyl diphosphate
-
alternative substrate, pH 7.5, 25°C
0.0000633
(2E,6E)-farnesyl diphosphate
pH 7.5, 25°C, D26R mutant with 0.5 mM MgCl2
0.0000766
(2E,6E)-farnesyl diphosphate
pH 7.5, 25°C, D26K mutant with 0.5 mM MgCl2
0.000366
(2E,6E)-farnesyl diphosphate
pH 7.5, 25°C, D26E mutant with 0.5 mM MgCl2
1.23
(2E,6E)-farnesyl diphosphate
pH 7.5, 25°C, wild type with 0.05 mM MgCl2
1.92
(2E,6E)-farnesyl diphosphate
pH 7.5, 25°C, wild type with 3 mM MgCl2
1.98
(2E,6E)-farnesyl diphosphate
pH 7.5, 25°C, wild type with 1 mM MgCl2
0.0025
(2E,6E)-farnesyl diphosphate
-
pH 7.5, 25°C, recombinant mutant H199A/E213A
0.0026
(2E,6E)-farnesyl diphosphate
-
pH 7.5, 25°C, recombinant mutant H43A and mutant E213A
2.5
(2E,6E)-farnesyl diphosphate
-
pH 7.5, 25°C, recombinant wild-type enzyme
2.5
(2E,6E)-farnesyl diphosphate
-
pH 7.5, 25°C, in the presence of 0.1% Triton
0.0026
farnesyl diphosphate
-
pH 7.5, 25°C, recombinant mutant H43A and mutant E213A
0.0025
isopentenyl diphosphate
-
pH 7.5, 25°C, recombinant mutant H199A/E213A
0.0026
isopentenyl diphosphate
-
pH 7.5, 25°C, recombinant mutant H43A and mutant E213A
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.1151
(2E,6E)-farnesyl diphosphate
pH 7.5, 25°C, D26R mutant with 0.5 mM MgCl2
0.1665
(2E,6E)-farnesyl diphosphate
pH 7.5, 25°C, D26K mutant with 0.5 mM MgCl2
0.5462
(2E,6E)-farnesyl diphosphate
pH 7.5, 25°C, D26E mutant with 0.5 mM MgCl2
820
(2E,6E)-farnesyl diphosphate
pH 7.5, 25°C, wild type with 0.05 mM MgCl2
4363
(2E,6E)-farnesyl diphosphate
pH 7.5, 25°C, wild type with 3 mM MgCl2
5351
(2E,6E)-farnesyl diphosphate
pH 7.5, 25°C, wild type with 1 mM MgCl2
3.79
(2E,6E)-farnesyl diphosphate
-
pH 7.5, 25°C, recombinant mutant H199A/E213A
6.25
(2E,6E)-farnesyl diphosphate
-
pH 7.5, 25°C, recombinant wild-type enzyme
0.0041
isopentenyl diphosphate
-
pH 7.5, 25°C, with (2E,6E)-farnesyl diphosphate
0.0232 - 0.0279
isopentenyl diphosphate
-
pH 7.5, 25°C, with (2E,6E)-8-O-(N-methyl-2-aminobenzoyl)-3,7-dimethyl-2,6-octandien-1-diphosphate
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00057
7-(2,6-dimethyl-8-diphospho-2,6-octadienyloxy)-8-methyl-4-trifluoromethyl-chromen-2-one geranyl diphosphate
-
(2E,6E)-farnesyl diphosphate as a substrate, pH 7.5, 25°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.2
(1-hydroxy-2-phenylethane-1,1-diyl)bis(phosphonic acid)
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.0011
(1-hydroxy-2-[3'-[(naphthalene-2-sulfonyl)amino][1,1'-biphenyl]-3-yl]ethane-1,1-diyl)bis(phosphonic acid)
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.0022
(2Z)-2-hydroxy-4-oxo-4-[[3-(3-phenoxyphenyl)propyl]amino]but-2-enoic acid
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.0005
(2Z)-2-hydroxy-4-[3-[3-(octyloxy)phenoxy]phenyl]-4-oxobut-2-enoic acid
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.00051
(2Z)-2-hydroxy-4-[4-(octyloxy)phenyl]-4-oxobut-2-enoic acid
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.00056
(2Z)-4-([3-[3-(hexyloxy)phenyl]propyl]amino)-2-hydroxy-4-oxobut-2-enoic acid
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.0019
(2Z)-4-[3-[3-(decyloxy)phenoxy]phenyl]-2-hydroxy-4-oxobut-2-enoic acid
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.00024
(2Z)-4-[[3-([1,1'-biphenyl]-3-yl)propyl]amino]-2-hydroxy-4-oxobut-2-enoic acid
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.048
1-(2-hydroxy-2,2-diphosphonoethyl)-3-phenylpyridin-1-ium
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.027
1-[[3-(hexyloxy)phenyl]methyl]-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.024
2-(2-[[5-(1-benzofuran-2-yl)-4-phenyl-4H-1,2,4-triazol-3-yl]sulfanyl]acetamido)benzoic acid
Escherichia coli
pH 7.5, 25°C
0.0022
2-hydroxy-6-(undecyloxy)benzoic acid
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.045
2-[[(2E)-2-cyano-3-[1-[(naphthalen-1-yl)methyl]-1H-indol-3-yl]prop-2-enoyl]amino]benzoic acid
Escherichia coli
pH 7.5, 25°C
0.025
2-[[(2E)-2-cyano-3-[3-[(4-fluorophenyl)methoxy]phenyl]prop-2-enoyl]amino]benzoic acid
Escherichia coli
pH 7.5, 25°C
0.15
2-[[3-(3,4-dimethylphenoxy)phenyl]carbamoyl]benzoic acid
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.034
3-(dibenzo[b,d]furan-4-yl)-1-(2,2-diphosphonoethyl)pyridin-1-ium
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.12
3-([1,1'-biphenyl]-2-yl)-1-(2,2-diphosphonoethyl)pyridin-1-ium
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.068
3-([1,1'-biphenyl]-3-yl)-1-(2,2-diphosphonoethyl)pyridin-1-ium
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.01
3-([1,1'-biphenyl]-3-yl)-1-(2-hydroxy-2,2-diphosphonoethyl)pyridin-1-ium
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.035
3-([1,1'-biphenyl]-4-yl)-1-(2,2-diphosphonoethyl)pyridin-1-ium
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.49
3-fluoro-1-(2-hydroxy-2,2-diphosphonoethyl)pyridin-1-ium
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.089
3-[(2E)-3,7-dimethylocta-2,6-dien-1-yl]-1-(2,2-diphosphonoethyl)pyridin-1-ium
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.013
4-(dibenzo[b,d]furan-4-yl)-1-(2-hydroxy-2,2-diphosphonoethyl)pyridin-1-ium
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.021
4-([1,1'-biphenyl]-3-yl)-1-(2,2-diphosphonoethyl)pyridin-1-ium
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.028
4-([1,1'-biphenyl]-4-yl)-1-(2,2-diphosphonoethyl)pyridin-1-ium
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.0032
4-[3-[([1,1'-biphenyl]-4-carbonyl)amino]phenoxy]benzene-1,2-dicarboxylic acid
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.00004
5-benzyl-3-[1-(4-cyclohexylanilino)ethenyl]-4-hydroxy-5,6-dihydropyridin-2(1H)-one
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.00063
5-benzyl-4-hydroxy-3-[1-[4-(1H-imidazol-1-yl)anilino]ethenyl]-5,6-dihydropyridin-2(1H)-one
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.0005
5-benzyl-N-(4-cyclohexylphenyl)-4-hydroxy-2-oxo-2,5-dihydro-1H-pyrrole-3-carboxamide
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.019
5-benzyl-N-[4-(hexyloxy)phenyl]-4-hydroxy-2-oxo-2,5-dihydro-1H-pyrrole-3-carboxamide
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.001
5-bromo-2-[4-(6-chloro-2,3-dihydro-1H-indole-1-sulfonyl)benzamido]benzoic acid
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.0088
6-benzyl-4-hydroxy-3-[1-[4-(1H-imidazol-1-yl)anilino]ethenyl]-5,6-dihydropyridin-2(1H)-one
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.01166
MAC-0110792
Escherichia coli
pH and temperature not specified in the publication
0.00139
MAC-0557874
Escherichia coli
pH and temperature not specified in the publication
0.071
N,N'-bis(6-chloro-1,3-benzothiazol-2-yl)methanedisulfonamide
Escherichia coli
pH 7.5, temperature not specified in the publication
0.002
N-(3,5-dichlorophenyl)-4-hydroxy-2-oxo-5-phenyl-2,5-dihydro-1H-pyrrole-3-carboxamide
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.024
N-(4-chlorophenyl)-4-hydroxy-2-oxo-5-phenyl-2,5-dihydro-1H-pyrrole-3-carboxamide
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.058
N-(4-cyclohexylphenyl)-4-hydroxy-2-oxo-2,5-dihydro-1H-pyrrole-3-carboxamide
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.00016
N-(4-cyclohexylphenyl)-4-hydroxy-2-oxo-5-(2-phenylethyl)-2,5-dihydro-1H-pyrrole-3-carboxamide
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.0035
N-(4-cyclohexylphenyl)-4-hydroxy-2-oxo-5-phenyl-2,5-dihydro-1H-pyrrole-3-carboxamide
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.00012
N-([1,1'-biphenyl]-4-yl)-4-hydroxy-2-oxo-5-(2-phenylethyl)-2,5-dihydro-1H-pyrrole-3-carboxamide
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.0032
N-[3-[3,4-di(prop-1-en-2-yl)phenoxy]phenyl][1,1'-biphenyl]-4-carboxamide
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.0048
N1,N4-bis[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]-2-nitrobenzene-1,4-dicarboxamide
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.66
[1-hydroxy-2-(pyridin-3-yl)ethane-1,1-diyl]bis(phosphonic acid)
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.00069
[1-hydroxy-2-([1(1),2(1):2(3),3(1)-terphenyl]-1(3)-yl)ethane-1,1-diyl]bis(phosphonic acid)
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.002
[1-hydroxy-2-([1(1),2(1):2(3),3(1)-terphenyl]-1(4)-yl)ethane-1,1-diyl]bis(phosphonic acid)
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
-
0.00091
[1-hydroxy-2-([1(1),2(1):2(4),3(1)-terphenyl]-1(3)-yl)ethane-1,1-diyl]bis(phosphonic acid)
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.0013
[1-hydroxy-2-[([1(1),2(1):2(3),3(1)-terphenyl]-1(3)-yl)oxy]ethane-1,1-diyl]bis(phosphonic acid)
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.0031
[1-hydroxy-3-([1(1),2(1):2(2),3(1)-terphenyl]-1(3)-yl)propane-1,1-diyl]bis(phosphonic acid)
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.0055
[1-hydroxy-3-([1(1),2(1):2(3),3(1)-terphenyl]-1(3)-yl)propane-1,1-diyl]bis(phosphonic acid)
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.01
[1-hydroxy-3-([1(1),2(1):2(4),3(1)-terphenyl]-1(3)-yl)propane-1,1-diyl]bis(phosphonic acid)
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.0068
[2-([1,1'-biphenyl]-3-yl)-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.00059
[2-[3-(dibenzo[b,d]furan-4-yl)phenyl]-1-hydroxy-1,1-ethanediyl]bis(phosphonic acid)
Escherichia coli
pH 7.5, 25°C
0.00059
[2-[3-(dibenzo[b,d]furan-4-yl)phenyl]-1-hydroxyethane-1,1-diyl]bis(phosphonic acid)
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.087
[3-(3,4-dichlorophenyl)-4,5-dihydro-1,2-oxazole-5,5-diyl]bis(phosphonic acid)
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.012
[3-[4-(dibenzo[b,d]furan-4-yl)phenyl]-1-hydroxypropane-1,1-diyl]bis(phosphonic acid)
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.069
[4-([1,1'-biphenyl]-4-yl)butane-1,1-diyl]bis(phosphonic acid)
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.0018
[hydroxy([1(1),2(1):2(3),3(1)-terphenyl]-1(3)-yl)methylene]bis(phosphonic acid)
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.0078
[[(9-ethyl-9H-carbazol-3-yl)amino](hydroxy)methylene]bis(phosphonic acid)
Escherichia coli
pH and temperature not specified in the publication, mutant enzyme Y246D
0.071
3-[5-(5,6-dihydrobenzimidazo[1,2-c]quinazolin-6-yl)-2,5-dihydrofuran-2-yl]benzenesulfonamide
Escherichia coli
-
0.0013
farnesyl thiodiphosphate
Escherichia coli
-
pH 7.5, 25°C, versus (2E,6E)-farnesyl diphosphate
0.0024 - 0.0039
farnesyl thiodiphosphate
Escherichia coli
-
pH 7.5, 25°C, versus (2E,6E)-8-O-(N-methyl-2-aminobenzoyl)-3,7-dimethyl-2,6-octandien-1-diphosphate
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
7.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
25
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
physiological function
physiological function
metabolism
an essential enzyme in the biosynthesis of bacterial cell wall
metabolism
essential enzyme in the biosynthesis of the bacterial cell wall
metabolism
the enzyme is responsible for the biogenesis of undecaprenyl phosphate, an indispensable glycosyl carrier lipid in bacterial cell wall biosynthesis
physiological function
bactoprenyl diphosphate (BPP), a two-E eight-Z configuration C55 isoprenoid, serves as a critical anchor for the biosynthesis of complex glycans central to bacterial survival and pathogenesis. BPP is formed by the polymerase undecaprenyl diphosphate synthase (UppS), which catalyzes the elongation of a single farnesyl diphosphate (FPP) with eight Z-configuration isoprene units from eight isopentenyl diphosphates
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
physiological function
-
expression of UPPS in the yeast mutant rer2DELTA, lacking undecaprenyl diphosphate synthase, complements the growth and the hypoglycosylation of carboxypeptidase Y defects. Mutant cells expressing UPPS synthesize dolichyl phosphate of chain length C55 and utilize it to form Man-P-(55)Dol in vitro and in vivo, and they synthesize N-linked glycoprotein
physiological function
-
UPPS is a cis- and trans-type prenyltransferase catalyzing consecutive condensation reactions of FPP with specific numbers of IPP to generate linear products with designate chain lengths, UPPS utilizes a concerted mechanism for IPP condensation, structures and mechanisms of the cis-prenyltransferase undecaprenyl diphosphate synthase, overview. Structures of different forms of UPPS with or without ligands reveal conformational changes upon substrate binding, catalysis and product release. A disordered loop in Escherichia coli UPPS, invisible in crystal structures without ligand, is essential for catalysis
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homodimer
dimer
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
purified recombinant wild-type and mutant D26A enzymes in complex with Mg2+, isopentenyl diphosphate and substrate analogue farnesyl thiodiphosphate, protein solution containing 10 mg/ml protein in 25 mM Tris-HCl, pH 7.5, 150 mM NaCl, and 0.03% Triton X-100, is mixed with dried MgCl2 and isopentenyl diphosphate powder, hanging drop vapour diffusion method, 0.002 ml of the final protein solution with equal volume of mother liquor containing 20% ethylene glycol, 2-5% PEG 35000, equilibration against 0.5 ml mother liquor at room temperature, 2 days, soaking in cryoprotectant containing 2.5 mM MgCl2, 2.5 mM isopentenyl diphosphate, 30% ethylene glycol, and 5% PEG 35000 for 1 day, X-ray diffraction strcture determination and analysis at 1.9-2.2 A resolution, molecular modeling
in complex with farnesyl diphosphate. Virtual screening of inhibitors from a library of 58,635 compounds, modelling of inhibitors N,N'-bis(6-chloro-1,3-benzothiazol-2-yl)methanedisulfonamide and 3-[5-(5,6-dihydrobenzimidazo[1,2-c]quinazolin-6-yl)-2,5-dihydrofuran-2-yl]benzenesulfonamide into structure
purified His-tagged wild-type enzyme in complex with Mg2+, sulfates, and 2 molecules of Triton X-100, hanging drop vapour diffusion method, 0.002 ml protein solution containing 10 mg/ml protein, 2% Triton X-100, 5 mM MgCl2, and 0.66 mM farnesyl diphosphate, is mixed with equal volume of mother liquid containing 0.01 M CoCl2, 0.1 M MES, pH 6.5, and 1.8 M ammonium sulfate, equilibration against 0.2 ml mother liquid at 25°C, 10 days, X-ray diffraction structure determination and analysis at 1.73 A resolution, modeling
-
purified His-tagged wild-type enzyme, hanging drop vapour diffusion method, high concentration of sulfate or phosphate in the mother liquid to prevent binding of Triton X-100 or substrates during crystallization, 0.002 ml mother liquid containing 25% ethylene glycol, pH 7.5, mixed with 0.002 ml protein solution containing 10 mg/ml protein, 1 mM peptide, 0.05% Triton X-100, and 0.5 mM MgCl2, equilibration against 0.2 ml mother liquid at 25°C, 5 days, crystals are then soaked in mother liquid containing 0.23 mM farnesyl diphosphate, X-ray diffraction structure determination and analysis at 2.4 A resolution, modeling
-
purified recombinant wild-type and mutant D26A enzymes in complex with Mg2+, isopentenyl diphosphate and substrate analogue farnesyl thiodiphosphate, protein solution containing 10 mg/ml protein in 25 mM Tris-HCl, pH 7.5, 150 mM NaCl, and 0.03% Triton X-100, is mixed with dried MgCl2 and isopentenyl diphosphate powder, hanging drop vapour diffusion method, 0.002 ml of the final protein solution with equal volume of mother liquor containing 20% ethylene glycol, 2-5% PEG 35000, equilibration against 0.5 ml mother liquor at room temperature, 2 days, soaking in cryoprotectant containing 2.5 mM MgCl2, 2.5 mM isopentenyl diphosphate, 30% ethylene glycol, and 5% PEG 35000 for 1 day, X-ray diffraction strcture determination and analysis at 1.9-2.2 A resolution, molecular modeling
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A143V
the C30 intermediate is formed to a greater extent and is longer lived in the process catalyzed by the A69L mutant
A69L
the small side chain of Ala-69 is required for rapid elongation to the C55 product
D26A
site-directed mutagenesis, altered Mg2+ binding and about 1000fold reduced activity compared to the wild-type enzyme
D26E
site-directed mutagenesis, altered Mg2+ binding and over 10000fold reduced activity compared to the wild-type enzyme
D26K
site-directed mutagenesis, altered Mg2+ binding and about 10000fold reduced activity compared to the wild-type enzyme
D26R
site-directed mutagenesis, altered Mg2+ binding and over 10000fold reduced activity compared to the wild-type enzyme
H103A
the product distributions formed by the use of the I62A, V105A, and H103A mutants are similar to those observed for wild-type UPPs
I62A
the product distributions formed by the use of the I62A, V105A, and H103A mutants are similar to those observed for wild-type UPPs
L137A
catalysis results in predominantly the formation of the C70 polymer rather than the C55 polymer
S71A
V105A
the product distributions formed by the use of the I62A, V105A, and H103A mutants are similar to those observed for wild-type UPPs
D150A
D218A
-
turnover-number is about 9% of the activity of the wild-type enzyme, Km value for farnesyl diphosphate is equal to that of the wild-type enzyme, Km-value for isopentenyl diphosphate is comparable to that of the wild-type enzyme
D26A
D26E
site-directed mutagenesis, altered Mg2+ binding and over 10000fold reduced activity compared to the wild-type enzyme
D26K
site-directed mutagenesis, altered Mg2+ binding and about 10000fold reduced activity compared to the wild-type enzyme
D26R
site-directed mutagenesis, altered Mg2+ binding and over 10000fold reduced activity compared to the wild-type enzyme
DELTAS72
-
loop-shortening mutant. Change of the length of the loop 72-83 impairs the ability of conformational change and causes remarkably lower activity of UPPs
DELTAS83
-
loop-shortening mutant. Change of the length of the loop 72-83 impairs the ability of conformational change and causes remarkably lower activity of UPPs
DELTAV82S83
-
loop-shortening mutant. Change of the length of the loop 72-83 impairs the ability of conformational change and causes remarkably lower activity of UPPs
E213A
E73A
E81A
turnover-number is 16% of that of the wild-type enzyme, Km-value for farnesyl diphosphate is equal to that of the wild-type enzyme, the Km-value for isopentenyl diphosphate is 21.5fold higher than that of the wild-type enzyme
F89A
H199A
-
site-directed mutagenesis, activity is similar to the wild-type enzyme
H199A/E213A
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme
H43A
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme
L137A
mutant enzyme produces C55-polyprenyl diphosphate, C60-polyprenyl diphosphate and C65-polyprenyl diphosphate in the ratio 55:41:4 in presence of Triton, compared to the wild-type enzyme which produces C55-polyprenyl diphosphate as the major product. In absence of Triton the mutant enzyme produces C70 and C75-polyprenyl diphosphate is the major products
L85A
L88A
N74A
turnover-number is less than 1% of that of the wild-type enzyme, Km-value for farnesyl diphosphate is equal to that of the wild-type enzyme, the Km-value for isopentenyl diphosphate is 2fold higher than that of the wild-type enzyme
R77A
turnover-number is less than 1% of that of the wild-type enzyme, Km-value for farnesyl diphosphate is 4fold higher than that of the wild-type enzyme, the Km-value for isopentenyl diphosphate is 3.8fold higher than that of the wild-type enzyme
S71A
turnover-number is 4.4% of that of the wild-type enzyme, Km-value for farnesyl diphosphate is 2.5fold higher than that of the wild-type enzyme, the Km-value for isopentenyl diphosphate is 32.4fold higher than that of the wild-type enzyme
W149F
-
turnover-number is 68% of that of the wild-type enzyme, Km-value for farnesyl diphosphate is 1.75fold higher than that of the wild-type enzyme, Km-value for isopentenyl diphosphate is 4.9fold higher than that of the wild-type enzyme
W207F
-
turnover-number is 60% of that of the wild-type enzyme, Km-value for farnesyl diphosphate is 8.5fold higher than that of the wild-type enzyme, Km-value for isopentenyl diphosphate is 5.6fold higher than that of the wild-type enzyme
W221F
-
turnover-number is 140% of that of the wild-type enzyme, Km-value for farnesyl diphosphate is 1.3fold higher than that of the wild-type enzyme, Km-value for isopentenyl diphosphate is 3.4fold higher than that of the wild-type enzyme
W31F
-
turnover-number is 44% of that of the wild-type enzyme,Km-value for farnesyl diphosphate is 5fold higher than that of the wild-type enzyme, Km-value for isopentenyl diphosphate is 1.4fold higher than that of the wild-type enzyme
W75A
turnover-number is 4.4% of that of the wild-type enzyme, Km-value for farnesyl diphosphate is 8fold higher than that of the wild-type enzyme, the Km-value for isopentenyl diphosphate is 11.2fold higher than that of the wild-type enzyme
W75F
-
turnover-number is 44% of that of the wild-type enzyme, Km-value for farnesyl diphosphate is 4.5fold higher than that of the wild-type enzyme, Km-value for isopentenyl diphosphate is 6.3fold higher than that of the wild-type enzyme
W91F
-
turnover-number is equal to that of the wild-type enzyme, Km-value for farnesyl diphosphate is equal to that of the wild-type enzyme, Km-value for isopentenyl diphosphate is 1.8fold higher than that of the wild-type enzyme
additional information
-
loop-shortening mutants with deletion of V82 and S83 or S72 also adopt an open conformation with the loop stretched, although they show decreased intrinsic fluorescence with (2E,6E)-farnesyl diphosphate bound, similar to that seen in the wild-type enzyme
D150A
-
turnover-number is 44% of the activity of the wild-type enzyme, Km value for farnesyl diphosphate is equal to that of the wild-type enzyme, Km-value for isopentenyl diphosphate is about 50fold higher than that of the wild-type enzyme
D150A
-
turnover-number is 44% of the activity of the wild-type enzyme, Km value for (2E,6E)-farnesyl diphosphate is equal to that of the wild-type enzyme, Km-value for isopentenyl diphosphate is about 50fold higher than that of the wild-type enzyme
D26A
-
turnover-number is less than 1% of that of the wild-type enzyme, Km value for farnesyl diphosphate is comparable to that of the wild-type enzyme, Km-value for isopentenyl diphosphate is 3.5fold higher than that of the wild-type enzyme
D26A
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme
D26A
site-directed mutagenesis, altered Mg2+ binding and about 1000fold reduced activity compared to the wild-type enzyme
D26A
-
the mutant shows altered Mg2+ binding compared to the wild-type enzyme
E213A
-
turnover-number is less than 1% of the activity of the wild-type enzyme, Km value for farnesyl diphosphate is 1.75fold higher than that of the wild-type enzyme, Km-value for isopentenyl diphosphate is about 68.3fold higher than that of the wild-type enzyme
E213A
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme
E73A
-
turnover-number is 12% of that of the wild-type enzyme, Km value for farnesyl diphosphate is equal to that of the wild-type enzyme, Km-value for isopentenyl diphosphate is about 4fold higher than that of the wild-type enzyme
E73A
turnover-number is 12% of that of the wild-type enzyme, Km-value for farnesyl diphosphate is equal to that of the wild-type enzyme, the Km-value for isopentenyl diphosphate is 3.9fold higher than that of the wild-type enzyme
F89A
-
site-directed mutagenesis, mutant shows highly increased Km for isopentenyl diphosphate with farnesyl diphosphate and slightly with geranylgeranyl diphosphate compared to the wild-type enzyme
F89A
-
mutation increases (2E,6E)-farnesyl diphosphate and geranylgeranyl diphosphate Km values, indicating that these amino acids are important for substrate binding, but do not determine substrate specificity
L85A
-
site-directed mutagenesis, mutant shows highly increased Km for isopentenyl diphosphate with farnesyl diphosphate and slightly with geranylgeranyl diphosphate compared to the wild-type enzyme
L85A
-
mutation increases (2E,6E)-farnesyl diphosphate and geranylgeranyl diphosphate Km values, indicating that these amino acids are important for substrate binding, but do not determine substrate specificity
L88A
-
site-directed mutagenesis, mutant shows highly increased Km for isopentenyl diphosphate with farnesyl diphosphate and slightly with geranylgeranyl diphosphate compared to the wild-type enzyme
L88A
-
mutation increases (2E,6E)-farnesyl diphosphate and geranylgeranyl diphosphate Km values, indicating that these amino acids are important for substrate binding, but do not determine substrate specificity
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
inactivation by irradiation with UV light in presence of (E,E)-(2-diazo-3-trifluoropropionyloxy)geranyl diphosphate, (E,E)-farnesyl diphosphate protects, isopentenyl diphosphate and Mg2+ are required for inactivation in presence of the photolabile substrate
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, dialysis, and gel filtration
recombinant His-tagged enzyme from Escherichia coli strain C41 by nickel affinity chromatography, dialysis, and gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene upps, recombinant expression of His-tagged enzyme in Escherichia coli strain C41
gene uppS, recombinant N-terminally His-tagged enzyme expression in Escherichia coli strain BL21(DE3)
expression in Escherichia coli
expression of mutant enzmyes W31F, W75F, W91F, W149F, W207F, and W221F as His-tag fusion proteins using Escherichia coli BL21 as host cells
-
gene uppS, expression of GFP-tagged UPPS in CHO cell endoplasmic reticulum, expression in Saccharomyces cerevisiae microsomes, ability of the Escherichia coli undecaprenyl pyrophosphate synthase to complement the loss of the yeast cis isoprenyltransferase in the rer2DELTA mutant
-
overexpression of His-tagged wild-type and mutant enzymes in strain BL21(DE3)
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pharmacology
pharmacology
the enzyme generate undecaprenyl pyrophosphate. The latter serves as a lipid carrier for peptidoglycan synthesis, thus representing an important target in the antibacterial drug design
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Baba, T.; Muth, J.; Allen, C.M.
Photoaffinity labeling of undecaprenyl pyrophosphate synthetase with a farnesyl pyrophosphate analogue
J. Biol. Chem.
260
10467-10473
1985
Escherichia coli
Fujisaki, S.; Nishino, T.; Katasuki, H.
Isoprenoid synthesis in Escherichia coli. Separation and partial purification of four enzymes involved in the synthesis
J. Biochem.
99
1327-1337
1986
Escherichia coli
Pan, J.J.; Chiou, S.T.; Liang, P.H.
Product distribution and pre-steady-state kinetic analysis of Escherichia coli undecaprenyl pyrophosphate synthase reaction
Biochemistry
39
10936-10942
2000
Escherichia coli
Shimizu, N.; Koyama, T.; Ogura, K.
Molecular cloning, expression, and purification of undecaprenyl diphosphate synthase. No sequence similarity between E- and Z-prenyl diphosphate synthases
J. Biol. Chem.
273
19476-19481
1998
Escherichia coli, Micrococcus luteus (O82827), Micrococcus luteus B-P 26 (O82827), Micrococcus luteus B-P 26
Ko, T.P.; Chen, Y.K.; Robinson, H.; Tsai, P.C.; Gao, Y.G.; Chen, A.P.C.; Wang, A.H.J.; Liang, P.H.
Mechanism of product chain length determination and the role of a flexible loop in Escherichia coli undecaprenyl-pyrophosphate synthase catalysis
J. Biol. Chem.
276
47474-47482
2001
Escherichia coli, Escherichia coli (P60472)
Chen, Y.H.; Chen, A.P.C.; Chen, C.T.; Wang, A.H.J.; Liang, P.H.
Probing the conformational change of Escherichia coli undecaprenyl pyrophosphate synthase during catalysis using an inhibitor and tryptophan mutants
J. Biol. Chem.
277
7369-7376
2002
Escherichia coli
Pan, J.J.; Yang, L.W.; Liang, P.H.
Effect of site-directed mutagenesis of the conserved aspartate and glutamate on E. coli undecaprenyl pyrophosphate synthase catalysis
Biochemistry
39
13856-13861
2000
Escherichia coli
Chen, A.P.; Chang, S.Y.; Lin, Y.C.; Sun, Y.S.; Chen, C.T.; Wang, A.H.; Liang, P.H.
Substrate and product specificities of cis-type undecaprenyl pyrophosphate synthase
Biochem. J.
386
169-176
2005
Escherichia coli
Chang, S.Y.; Ko, T.P.; Liang, P.H.; Wang, A.H.
Catalytic mechanism revealed by the crystal structure of undecaprenyl pyrophosphate synthase in complex with sulfate, magnesium, and triton
J. Biol. Chem.
278
29298-29307
2003
Escherichia coli
Guo, R.T.; Ko, T.P.; Chen, A.P.; Kuo, C.J.; Wang, A.H.; Liang, P.H.
Crystal structures of undecaprenyl pyrophosphate synthase in complex with magnesium, isopentenyl pyrophosphate, and farnesyl thiopyrophosphate: roles of the metal ion and conserved residues in catalysis
J. Biol. Chem.
280
20762-20774
2005
Escherichia coli, Escherichia coli (P60472)
Chang, S.Y.; Ko, T.P.; Chen, A.P.; Wang, A.H.; Liang, P.H.
Substrate binding mode and reaction mechanism of undecaprenyl pyrophosphate synthase deduced from crystallographic studies
Protein Sci.
13
971-978
2004
Escherichia coli
Takahashi, S.; Koyama, T.
Structure and function of cis-prenyl chain elongating enzymes
Chem. Rec.
6
194-205
2006
Escherichia coli, Micrococcus luteus (O82827), Micrococcus luteus B-P 26 (O82827), Micrococcus luteus B-P 26
Guo, R.T.; Cao, R.; Liang, P.H.; Ko, T.P.; Chang, T.H.; Hudock, M.P.; Jeng, W.Y.; Chen, C.K.; Zhang, Y.; Song, Y.; Kuo, C.J.; Yin, F.; Oldfield, E.; Wang, A.H.
Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases
Proc. Natl. Acad. Sci. USA
104
10022-10027
2007
Escherichia coli
Kuo, C.; Guo, R.; Lu, I.; Liu, H.; Wu, S.; Ko, T.; Wang, A.H.; Liang, P.
Structure-based inhibitors exhibit differential activities against Helicobacter pylori and Escherichia coli undecaprenyl pyrophosphate synthases
J. Biomed. Biotechnol.
2008
841312
2008
Escherichia coli, Escherichia coli (P60472), Helicobacter pylori, Helicobacter pylori (P55984)
Chang, S.Y.; Chen, Y.K.; Wang, A.H.; Liang, P.H.
Identification of the active conformation and the importance of length of the flexible loop 72-83 in regulating the conformational change of undecaprenyl pyrophosphate synthase
Biochemistry
42
14452-14459
2003
Escherichia coli
Chen, A.P.; Chen, Y.H.; Liu, H.P.; Li, Y.C.; Chen, C.T.; Liang, P.H.
Synthesis and application of a fluorescent substrate analogue to study ligand interactions for undecaprenyl pyrophosphate synthase
J. Am. Chem. Soc.
124
15217-15224
2002
Escherichia coli
Apfel, C.M.; Takacs, B.; Fountoulakis, M.; Stieger, M.; Keck, W.
Use of genomics to identify bacterial undecaprenyl pyrophosphate synthetase: cloning, expression, and characterization of the essential uppS gene
J. Bacteriol.
181
483-492
1999
Escherichia coli, Haemophilus influenzae (P44938), Haemophilus influenzae, Streptococcus pneumoniae R6
Teng, K.H.; Chen, A.P.; Kuo, C.J.; Li, Y.C.; Liu, H.G.; Chen, C.T.; Liang, P.H.
Fluorescent substrate analog for monitoring chain elongation by undecaprenyl pyrophosphate synthase in real time
Anal. Biochem.
417
136-141
2011
Escherichia coli
Teng, K.; Liang, P.
Structures, mechanisms and inhibitors of undecaprenyl diphosphate synthase: A cis-prenyltransferase for bacterial peptidoglycan biosynthesis
Bioorg. Chem.
43
51-57
2012
Escherichia coli, Micrococcus luteus, Micrococcus luteus B-P 26, Streptococcus pneumoniae (Q97SR4)
Rush, J.; Matveev, S.; Guan, Z.; Raetz, C.; Waechter, C.
Expression of functional bacterial undecaprenyl pyrophosphate synthase in the yeast rer2DELTA mutant and CHO cells
Glycobiology
20
1585-1593
2010
Escherichia coli
Dodbele, S.; Martinez, C.D.; Troutman, J.M.
Species differences in alternative substrate utilization by the antibacterial target undecaprenyl pyrophosphate synthase
Biochemistry
53
5042-5050
2014
Bacteroides fragilis (Q5LI17), Bacteroides fragilis, Bacteroides fragilis ATCC 25285 (Q5LI17), Escherichia coli (P60472), Escherichia coli, Escherichia coli DH5alpha (P60472), Vibrio vulnificus (A0A087IPJ7), Vibrio vulnificus, Vibrio vulnificus MO6-24/O (A0A087IPJ7)
Zhu, W.; Wang, Y.; Li, K.; Gao, J.; Huang, C.H.; Chen, C.C.; Ko, T.P.; Zhang, Y.; Guo, R.T.; Oldfield, E.
Antibacterial drug leads: DNA and enzyme multitargeting
J. Med. Chem.
58
1215-1227
2015
Staphylococcus aureus, Escherichia coli (P60472), Escherichia coli
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
Proc. Natl. Acad. Sci. USA
112
11048-11053
2015
Escherichia coli (P60472), Escherichia coli MC1061 (P60472), Staphylococcus aureus (A0A0H2XGF2), Staphylococcus aureus, Staphylococcus aureus USA300 (A0A0H2XGF2)
Czarny, T.L.; Brown, E.D.
A small-molecule screening platform for the discovery of inhibitors of undecaprenyl diphosphate synthase
ACS Infect. Dis.
2
489-499
2016
Bacillus subtilis (O31751), Bacillus subtilis 168 (O31751), Escherichia coli, Escherichia coli (P60472), Escherichia coli K12, Escherichia coli K12 (P60472), Staphylococcus aureus, Staphylococcus aureus (A0A0H2XGF2), Staphylococcus aureus Newman, Staphylococcus aureus USA300 (A0A0H2XGF2)
Jukic, M.; Rozman, K.; Gobec, S.
Recent advances in the development of undecaprenyl pyrophosphate synthase inhibitors as potential antibacterials
Curr. Med. Chem.
23
464-482
2016
Escherichia coli (P60472), Escherichia coli K12 (P60472)
Jukic, M.; Rozman, K.; Sova, M.; Barreteau, H.; Gobec, S.
Anthranilic acid inhibitors of undecaprenyl pyrophosphate synthase (UppS), an essential enzyme for bacterial cell wall biosynthesis
Front. Microbiol.
9
3322
2018
Escherichia coli (P60472), Escherichia coli, Escherichia coli K12 (P60472)
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