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Literature summary for 2.5.1.31 extracted from

  • 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 (2008), J. Biomed. Biotechnol., 2008, 841312.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.5.1.31

Application

Application Comment Organism
medicine enzyme represents a potential target for developing new antibiotics Helicobacter pylori

Cloned(Commentary)

Cloned (Comment) Organism
expressed in Escherichia coli Escherichia coli
expressed in Escherichia coli Helicobacter pylori
expression in Escherichia coli Escherichia coli
expression in Escherichia coli Helicobacter pylori

Crystallization (Commentary)

Crystallization (Comment) Organism
C234A UPPS mutant to prevent intra-molecular disulfide bond formed during the long period of crystallization process is crystallized using the hanging drop method. The protein is a dimer and each subunit contains a catalytic domain and a pairing domain. Two subunits are tightly associated through the central beta-sheet and a pair of long alpha-helices. Helicobacter pylori UPPS has a 1.5-turn shorter alpha5 helix in the dimer interface. This may weaken the dimer formation for Helicobacter pylori UPPS. The catalytic domain is composed of six beta-strands and four beta-helices and the central tunnel-shaped active site is surrounded by 2 alpha-helices and 4 beta-strands Helicobacter pylori
crystal structure of Helicobacter pylori UPPS and mutant by hanging drop method Helicobacter pylori
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 Escherichia coli
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 Helicobacter pylori

Protein Variants

Protein Variants Comment Organism
C234A kinetic data similar to wild-type. Crystallization data Helicobacter pylori
C234A kinetik data similar to wild-type. Crystallization data Escherichia coli
C234A C234A UPPS mutant is crystallized using the hanging drop method, C234A has unchanged kinetic properties compared to wild-type Helicobacter pylori
C234A site-directed mutagenesis, mutation to prevent intramolecular disulfide bond formed during the long period of crystallization process Helicobacter pylori

Inhibitors

Inhibitors Comment Organism Structure
3-[5-(5,6-dihydrobenzimidazo[1,2-c]quinazolin-6-yl)-2,5-dihydrofuran-2-yl]benzenesulfonamide barely inhibits UPPS of Escherichia coli; barely inhibits UPPS of Escherichia coli; i.e. HTS04781. contrary to Helicobacter pylori, HTS04781 is almost not inhibitory in Escherichia coli Escherichia coli
3-[5-(5,6-dihydrobenzimidazo[1,2-c]quinazolin-6-yl)-2,5-dihydrofuran-2-yl]benzenesulfonamide i.e. HTS04781, crystallization data. The sulfonamide group forms H-bonds with Gly16 and Arg26 and the N atom in the tetracyclic ring is hydrogen bound to the main chain of Met12. Extensive hydrophobic interactions are found between the tetracyclic ring with the surrounding residues including Met12, His30, Gly33 and Val34 Helicobacter pylori
additional information virtual screening of inhibitors from a library of 58635 compounds performed Helicobacter pylori
N,N'-bis(6-chloro-1,3-benzothiazol-2-yl)methanedisulfonamide barely inhibits UPPS of Escherichia coli; i.e. BTB06061 Escherichia coli
N,N'-bis(6-chloro-1,3-benzothiazol-2-yl)methanedisulfonamide i.e. BTB06061, crystallization data. The sulfur atom in the thiazole ring of BTB06061 may form H-bonds with Asn15 and His30 while the SO2 group is hydrogen bound with Met12. The aromatic rings of BTB06061 form hydrophobic interactions with the surrounding hydrophobic residues, including Val34, Leu37, Ala56 and Tyr79 Helicobacter pylori

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.00011
-
 (2E,6E)-farnesyl diphosphate wild-type Helicobacter pylori
0.00011
-
 farnesyl diphosphate wild-type, pH 7.5 Helicobacter pylori
0.00011
-
 (2E,6E)-farnesyl diphosphate wild type, pH 7.5, temperature not specified in the publication Helicobacter pylori
0.00015
-
 farnesyl diphosphate mutant C234A, pH 7.5 Helicobacter pylori
0.00015
-
 (2E,6E)-farnesyl diphosphate mutant C234A Helicobacter pylori
0.00015
-
 (2E,6E)-farnesyl diphosphate mutant C234A, pH 7.5, temperature not specified in the publication Helicobacter pylori
0.0092
-
 isopentenyl diphosphate wild-type Helicobacter pylori
0.0092
-
 isopentenyl diphosphate wild-type, pH 7.5 Helicobacter pylori
0.0092
-
 (2E,6E)-farnesyl diphosphate wild type, pH 7.5, temperature not specified in the publication Helicobacter pylori
0.0096
-
 isopentenyl diphosphate mutant C234A, pH 7.5 Helicobacter pylori
0.0096
-
 isopentenyl diphosphate mutant C234A Helicobacter pylori
0.0096
-
 (2E,6E)-farnesyl diphosphate mutant C234A, pH 7.5, temperature not specified in the publication Helicobacter pylori

Organism

Organism UniProt Comment Textmining
Escherichia coli
-
-
-
Escherichia coli P60472
-
-
Helicobacter pylori
-
-
-
Helicobacter pylori P55984
-
-

Purification (Commentary)

Purification (Comment) Organism
-
 Escherichia coli
-
 Helicobacter pylori

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
-
 Escherichia coli 8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
-
 ?
(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate
-
 Helicobacter pylori 8 diphosphate + ditrans,octacis-undecaprenyl diphosphate
-
 ?
(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate
-
 Escherichia coli diphosphate + di-trans,poly-cis-undecaprenyl diphosphate
-
 ?
(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate
-
 Helicobacter pylori diphosphate + ditrans,polycis-undecaprenyl diphosphate
-
 ?
farnesyl diphosphate + isopentenyl diphosphate
-
 Helicobacter pylori diphosphate + di-trans-poly-cis-undecaprenyl diphosphate
-
 ?

Subunits

Subunits Comment Organism
dimer crystal structure Helicobacter pylori
dimer each subunit contains a catalytic domain and a pairing domain Helicobacter pylori

Synonyms

Synonyms Comment Organism
undecaprenyl pyrophosphate synthase
-
 Escherichia coli
undecaprenyl pyrophosphate synthase
-
 Helicobacter pylori
UPPs
-
 Escherichia coli
UPPs
-
 Helicobacter pylori

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.2
-
 farnesyl diphosphate mutant C234A, pH 7.5 Helicobacter pylori
0.2
-
 isopentenyl diphosphate mutant C234A, co-substrate: farnesyl diphosphate Helicobacter pylori
0.2
-
 (2E,6E)-farnesyl diphosphate mutant C234A, co-substrate: isopentenyl diphosphate Helicobacter pylori
0.2
-
 (2E,6E)-farnesyl diphosphate mutant C234A, pH 7.5, temperature not specified in the publication Helicobacter pylori
0.22
-
 farnesyl diphosphate wild-type, pH 7.5 Helicobacter pylori
0.22
-
 isopentenyl diphosphate wild-type, co-substrate: farnesyl diphosphate Helicobacter pylori
0.22
-
 (2E,6E)-farnesyl diphosphate wild-type, co-substrate: isopentenyl diphosphate Helicobacter pylori
0.22
-
 (2E,6E)-farnesyl diphosphate wild type, pH 7.5, temperature not specified in the publication Helicobacter pylori

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
 assay at Escherichia coli
7.5
-
 assay at Helicobacter pylori

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.071
-
-
 Escherichia coli N,N'-bis(6-chloro-1,3-benzothiazol-2-yl)methanedisulfonamide
0.071
-
-
 Escherichia coli 3-[5-(5,6-dihydrobenzimidazo[1,2-c]quinazolin-6-yl)-2,5-dihydrofuran-2-yl]benzenesulfonamide
0.071
-
 pH 7.5 Escherichia coli N,N'-bis(6-chloro-1,3-benzothiazol-2-yl)methanedisulfonamide
0.071
-
 pH 7.5, temperature not specified in the publication Escherichia coli N,N'-bis(6-chloro-1,3-benzothiazol-2-yl)methanedisulfonamide
0.35
-
 pH 7.5 Helicobacter pylori N,N'-bis(6-chloro-1,3-benzothiazol-2-yl)methanedisulfonamide
0.35
-
 IC50 value of this compound is equal against the C234A mutant and wild-type Helicobacter pylori N,N'-bis(6-chloro-1,3-benzothiazol-2-yl)methanedisulfonamide
0.35
-
 pH 7.5, temperature not specified in the publication Helicobacter pylori N,N'-bis(6-chloro-1,3-benzothiazol-2-yl)methanedisulfonamide
0.362
-
 pH 7.5 Helicobacter pylori 3-[5-(5,6-dihydrobenzimidazo[1,2-c]quinazolin-6-yl)-2,5-dihydrofuran-2-yl]benzenesulfonamide
0.362
-
 IC50 value of this compound is equal against the C234A mutant and wild-type Helicobacter pylori 3-[5-(5,6-dihydrobenzimidazo[1,2-c]quinazolin-6-yl)-2,5-dihydrofuran-2-yl]benzenesulfonamide
0.362
-
 pH 7.5, temperature not specified in the publication Helicobacter pylori 3-[5-(5,6-dihydrobenzimidazo[1,2-c]quinazolin-6-yl)-2,5-dihydrofuran-2-yl]benzenesulfonamide