BRENDA - Enzyme Database show
show all sequences of 4.6.1.12

A structure-based approach to ligand discovery for 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase: a target for antimicrobial therapy

Ramsden, N.L.; Buetow, L.; Dawson, A.; Kemp, L.A.; Ulaganathan, V.; Brenk, R.; Klebe, G.; Hunter, W.N.; J. Med. Chem. 52, 2531-2542 (2009)

Data extracted from this reference:

Application
Application
Commentary
Organism
drug development
framework for the development of IspF inhibitors to generate lead compounds of therapeutic potential against microbial pathogens
Escherichia coli
Cloned(Commentary)
Commentary
Organism
expressed in Escherichia coli strain BL21 (DE3)
Escherichia coli
Crystallization (Commentary)
Crystallization
Organism
IspF-CDP complex, to 1.8 A resolution. IspF in complex with compound 6b, to 3.1 A resolution, belongs to space group I213 with unit cell parameter a = 144 A. IspF in complex with compound 7, to 2.7 A resolution, belongs to space group I213 with unit cell parameter a = 144.5 A. IspF in complex with cytosine arabinoside monophosphate, to 2.1 A resolution, belongs to space group P21 with unit cell parameters a = 88.8 A, b = 54.2 A, c = 118.4 A, beta = 95°. IspF in complex with 5-fluorocytidine, to 2.5 A resolution, belongs to space group C2 with unit cell parameters a = 104.68 A, b = 54.83 A, c = 88.51 A, beta = 99.66°. IspF in complex with cidofovir, to 2.8 A resolution, belongs to space group I213 with unit cell parameter a = 145.68 A
Escherichia coli
Inhibitors
Inhibitors
Commentary
Organism
Structure
2-amino-N-hydroxy-3-(1-H-indol-3-yl)-propionimidic acid
highest affinity of all the ligands examined, due to Zn2+-hydroxamate coordination, KD value of 0.0019 mM
Escherichia coli
4-amino-1-(3-O-phosphono-a-D-lyxofuranosyl)pyrimidin-2(1H)-one
-
Escherichia coli
4-amino-1-[(2S,3aS,4S,6R,6aR)-2-hydroxy-6-(hydroxymethyl)-2-oxidotetrahydrofuro[3,4-d][1,3,2]dioxaphosphol-4-yl]pyrimidin-2(1H)-one
KD value of 20.5 mM
Escherichia coli
4-amino-1-[(4aR,6R,7R,7aS)-2,7-dihydroxy-2-oxidotetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl]pyrimidin-2(1H)-one
KD value of 0.925 mM
Escherichia coli
5-fluorocytidine
KD value of 2.02 mM
Escherichia coli
Cidofovir
KD value of ca. 40 mM
Escherichia coli
Cytosine arabinoside monophosphate
KD value of 18.91 mM
Escherichia coli
additional information
5-(1,3-benzodioxol-5-ylamino)-5-oxopentanoic acid, 2-[(2,6-diaminopyrimidin-4-yl)sulfanyl]acetamide and 4-(5-amino-1,3,4-oxadiazol-2-yl)-1,2,5-oxadiazol-3-amine are inactive. Activity with compounds 2-amino-N-hydroxy-acetimidic acid, N-hydroxy-nicotinimidic acid, 5-bromo-thiophene-2-sulfonic acid amide, 4-bromobenzenesulfonamide and 4-(4-dimethylamino-phenylazo)-benzenesulfonamide are not measurable
Escherichia coli
Metals/Ions
Metals/Ions
Commentary
Organism
Structure
Mg2+
Mg2+ or Mn2+, positioned between the alpha- and beta-phosphates of the substrate, acts in concert with the Zn2+ to align and polarize the substrate for catalysis
Escherichia coli
Mn2+
Mg2+ or Mn2+, positioned between the alpha- and beta-phosphates of the substrate, acts in concert with the Zn2+ to align and polarize the substrate for catalysis
Escherichia coli
Zn2+
Zn2+-binding site, addition of a Zn2+-binding moiety may prove valuable in assisting the design of potent and selective inhibitors
Escherichia coli
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Escherichia coli
P62617
-
-
Purification (Commentary)
Commentary
Organism
-
Escherichia coli
Application (protein specific)
Application
Commentary
Organism
drug development
framework for the development of IspF inhibitors to generate lead compounds of therapeutic potential against microbial pathogens
Escherichia coli
Cloned(Commentary) (protein specific)
Commentary
Organism
expressed in Escherichia coli strain BL21 (DE3)
Escherichia coli
Crystallization (Commentary) (protein specific)
Crystallization
Organism
IspF-CDP complex, to 1.8 A resolution. IspF in complex with compound 6b, to 3.1 A resolution, belongs to space group I213 with unit cell parameter a = 144 A. IspF in complex with compound 7, to 2.7 A resolution, belongs to space group I213 with unit cell parameter a = 144.5 A. IspF in complex with cytosine arabinoside monophosphate, to 2.1 A resolution, belongs to space group P21 with unit cell parameters a = 88.8 A, b = 54.2 A, c = 118.4 A, beta = 95°. IspF in complex with 5-fluorocytidine, to 2.5 A resolution, belongs to space group C2 with unit cell parameters a = 104.68 A, b = 54.83 A, c = 88.51 A, beta = 99.66°. IspF in complex with cidofovir, to 2.8 A resolution, belongs to space group I213 with unit cell parameter a = 145.68 A
Escherichia coli
Inhibitors (protein specific)
Inhibitors
Commentary
Organism
Structure
2-amino-N-hydroxy-3-(1-H-indol-3-yl)-propionimidic acid
highest affinity of all the ligands examined, due to Zn2+-hydroxamate coordination, KD value of 0.0019 mM
Escherichia coli
4-amino-1-(3-O-phosphono-a-D-lyxofuranosyl)pyrimidin-2(1H)-one
-
Escherichia coli
4-amino-1-[(2S,3aS,4S,6R,6aR)-2-hydroxy-6-(hydroxymethyl)-2-oxidotetrahydrofuro[3,4-d][1,3,2]dioxaphosphol-4-yl]pyrimidin-2(1H)-one
KD value of 20.5 mM
Escherichia coli
4-amino-1-[(4aR,6R,7R,7aS)-2,7-dihydroxy-2-oxidotetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl]pyrimidin-2(1H)-one
KD value of 0.925 mM
Escherichia coli
5-fluorocytidine
KD value of 2.02 mM
Escherichia coli
Cidofovir
KD value of ca. 40 mM
Escherichia coli
Cytosine arabinoside monophosphate
KD value of 18.91 mM
Escherichia coli
additional information
5-(1,3-benzodioxol-5-ylamino)-5-oxopentanoic acid, 2-[(2,6-diaminopyrimidin-4-yl)sulfanyl]acetamide and 4-(5-amino-1,3,4-oxadiazol-2-yl)-1,2,5-oxadiazol-3-amine are inactive. Activity with compounds 2-amino-N-hydroxy-acetimidic acid, N-hydroxy-nicotinimidic acid, 5-bromo-thiophene-2-sulfonic acid amide, 4-bromobenzenesulfonamide and 4-(4-dimethylamino-phenylazo)-benzenesulfonamide are not measurable
Escherichia coli
Metals/Ions (protein specific)
Metals/Ions
Commentary
Organism
Structure
Mg2+
Mg2+ or Mn2+, positioned between the alpha- and beta-phosphates of the substrate, acts in concert with the Zn2+ to align and polarize the substrate for catalysis
Escherichia coli
Mn2+
Mg2+ or Mn2+, positioned between the alpha- and beta-phosphates of the substrate, acts in concert with the Zn2+ to align and polarize the substrate for catalysis
Escherichia coli
Zn2+
Zn2+-binding site, addition of a Zn2+-binding moiety may prove valuable in assisting the design of potent and selective inhibitors
Escherichia coli
Purification (Commentary) (protein specific)
Commentary
Organism
-
Escherichia coli
Other publictions for EC 4.6.1.12
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Temperature Optimum [°C]
Temperature Range [°C]
Temperature Stability [°C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [°C] (protein specific)
Temperature Range [°C] (protein specific)
Temperature Stability [°C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
747328
Liu
Crystal structure of IspF fro ...
Bacillus subtilis 168, Bacillus subtilis
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BSR20171370
2018
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749009
Mandal
Enhanced production of stevio ...
Stevia rebaudiana
Plant Physiol. Biochem.
89
100-106
2015
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1
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1
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730270
Jung
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Molecular and functional chara ...
Brassica rapa
J. Plant Biotechnol.
39
189-195
2012
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1
1
1
1
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730357
Kumar
2C-Methyl-D-erythritol 2,4-cyc ...
Stevia rebaudiana
Mol. Biol. Rep.
39
10971-10978
2012
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1
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1
1
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5
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1
1
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1
3
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3
-
-
730628
Zheng
-
Cloning and characterization o ...
Rauvolfia verticillata
Plant OMICS
4
82-90
2011
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-
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1
1
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1
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5
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1
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1
1
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1
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708124
Geist
Thiazolopyrimidine inhibitors ...
Arabidopsis thaliana, Escherichia coli, Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv, Plasmodium falciparum, Plasmodium falciparum NF54
ChemMedChem
5
1092-1101
2010
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2
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63
3
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5
2
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9
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2
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6
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3
1
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75
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2
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75
63
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3
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2
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6
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3
1
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714711
Narayanasamy
Synthesis of 4-diphosphocytidy ...
Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv
Chem. Biol.
17
117-122
2010
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2
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160
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706809
Battilana
The 1-deoxy-D: -xylulose 5-pho ...
Vitis vinifera x Vitis riparia, Vitis vinifera x Vitis vinifera
Theor. Appl. Genet.
118
653-669
2009
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2
2
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709435
Ramsden
A structure-based approach to ...
Escherichia coli
J. Med. Chem.
52
2531-2542
2009
-
1
1
1
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8
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3
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709487
Liu
-
A new 2-C-methyl-D-erythritol ...
Taxus x media
J. Med. Plant Res.
3
395-402
2009
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1
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1
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1
1
1
1
1
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691382
Sando
Cloning and characterization o ...
Hevea brasiliensis
Biosci. Biotechnol. Biochem.
72
2903-2917
2008
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1
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1
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694098
Chen
Molecular cloning and characte ...
Cephalotaxus harringtonia
Mol. Biol. Rep.
36
1749-1756
2008
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1
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1
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1
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695176
Narayanasamy
Chemoenzymatic synthesis of 4- ...
Mycobacterium tuberculosis, Mycobacterium tuberculosis Rv3582c
Tetrahedron Lett.
49
4461-4463
2008
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2
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680059
Baumgartner
-
Structure-based design and syn ...
Escherichia coli
Helv. Chim. Acta
90
1043-1068
2007
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682735
Calisto
Biosynthesis of isoprenoids in ...
Arabidopsis thaliana
Protein Sci.
16
2082-2088
2007
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1
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666594
Kim
-
Cloning and characterization o ...
Ginkgo biloba
Plant Cell Rep.
8
829-835
2006
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1
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672138
Lherbet
Absence of substrate channelin ...
Agrobacterium tumefaciens
Biochemistry
45
3548-3553
2006
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1
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675583
Illarionova
Nonmevalonate terpene biosynth ...
Plasmodium sp.
J. Org. Chem.
71
8824-8834
2006
-
2
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681826
Jin
-
Isolation and characterization ...
Taxus x media
Mol. Biol.
40
914-921
2006
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A double mutation of Escherich ...
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Structure of 2C-methyl-D-eryth ...
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Structure and catalytic mechan ...
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Structure of 2C-methyl-D-eryth ...
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Biosynthesis of terpenoids: Yg ...
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