Literature summary for 1.1.1.267 extracted from

Andaloussi, M.; Henriksson, L.M.; Wieckowska, A.; Lindh, M.; Bjoerkelid, C.; Larsson, A.M.; Suresh, S.; Iyer, H.; Srinivasa, B.R.; Bergfors, T.; Unge, T.; Mowbray, S.L.; Larhed, M.; Jones, T.A.; Karlen, A.
Design, synthesis, and X-ray crystallographic studies of alpha-aryl substituted fosmidomycin analogues as inhibitors of Mycobacterium tuberculosis 1-deoxy-D-xylulose 5-phosphate reductoisomerase (2011), J. Med. Chem., 54, 4964-4976.

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Crystallization (Commentary)

Crystallization (Comment)	Organism
MtDXR in complex with fosmidomycin alone or additionally with inhibitor 3-(N-hydroxyacetamido)-1-(3,4-dichlorophenyl)propylphosphonic acid or inhibitor 3-(N-hydroxyformamido)-1-(3,4-dichlorophenyl)propylphosphonic acid and NADPH, from 25% w/v PEG 3350, 0.2 M ammonium sulfate, and 0.1 M Bis-Tris, pH 5.7-5.9, a cryosolution consists of the screening solution and 25% glycerol, 75 mM NaCl including DMSO, dithiothreitol, cofactors Mn2+ and NADPH, and ligands, i.e. compounds 3-(N-hydroxyformamido)-1-(3,4-dichlorophenyl)propylphosphonic acid and 3-(N-hydroxyacetamido)-1-(3,4-dichlorophenyl)propylphosphonic acid, X-ray diffraction structure determination and analysis	Mycobacterium tuberculosis

Crystallization (Comment)

Organism

MtDXR in complex with fosmidomycin alone or additionally with inhibitor 3-(N-hydroxyacetamido)-1-(3,4-dichlorophenyl)propylphosphonic acid or inhibitor 3-(N-hydroxyformamido)-1-(3,4-dichlorophenyl)propylphosphonic acid and NADPH, from 25% w/v PEG 3350, 0.2 M ammonium sulfate, and 0.1 M Bis-Tris, pH 5.7-5.9, a cryosolution consists of the screening solution and 25% glycerol, 75 mM NaCl including DMSO, dithiothreitol, cofactors Mn2+ and NADPH, and ligands, i.e. compounds 3-(N-hydroxyformamido)-1-(3,4-dichlorophenyl)propylphosphonic acid and 3-(N-hydroxyacetamido)-1-(3,4-dichlorophenyl)propylphosphonic acid, X-ray diffraction structure determination and analysis

Mycobacterium tuberculosis

Inhibitors

Inhibitors	Comment	Organism
(3-(N-hydroxyacetamido)-1-phenyl)propylphosphonic acid	92% inhibition at 0.1 mM	Mycobacterium tuberculosis
3-(N-hydroxyacetamido)-1-(3,4-dichlorophenyl)propylphosphonic acid	-	Mycobacterium tuberculosis
3-(N-hydroxyformamido)-1-(2-bromophenyl)propylphosphonic acid	93% inhibition at 0.1 mM	Mycobacterium tuberculosis
3-(N-hydroxyformamido)-1-(3,4-dichlorophenyl)propylphosphonic acid	-	Mycobacterium tuberculosis
diethyl (1-(3,4-dichlorophenyl)-3-(N-hydroxyacetamido)propyl)phosphonate	-	Mycobacterium tuberculosis
diethyl (1-(3,4-dichlorophenyl)-3-(N-hydroxyformamido)propyl)phosphonate	-	Mycobacterium tuberculosis
ethyl hydrogen [1-(3,4-dichlorophenyl)-3-[formyl(hydroxy)amino]propyl]phosphonate	-	Mycobacterium tuberculosis
ethyl hydrogen [3-[acetyl(hydroxy)amino]-1-(3,4-dichlorophenyl)propyl]phosphonate	-	Mycobacterium tuberculosis
ethyl hydrogen [3-[acetyl(hydroxy)amino]-1-[2-(pyridin-3-yl)phenyl]propyl]phosphonate	20% inhibition at 0.1 mM	Mycobacterium tuberculosis
fosmidomycin	-	Mycobacterium tuberculosis
FR900098	-	Mycobacterium tuberculosis
additional information	design, synthesis, and X-ray crystallographic studies of alpha-aryl 3,4-dichlorophenyl-substituted fosmidomycin analogues as enzyme inhibitors. The introduction of a 3,4-dichlorophenyl group in the Calpha-position relative to the phosphonate group produces analogues that have a higher in vitro antimalarial activity than fosmidomycin	Mycobacterium tuberculosis
N-hydroxy-N-[2-(3-hydroxy-3-oxido-3,4-dihydro-1H-2,3-benzoxaphosphinin-4-yl)ethyl]acetamide	12% inhibition at 0.1 mM	Mycobacterium tuberculosis
[3-[acetyl(hydroxy)amino]-1-(2-bromophenyl)propyl]phosphonic acid	38% inhibition at 0.1 mM	Mycobacterium tuberculosis
[3-[acetyl(hydroxy)amino]-1-(2-cyanophenyl)propyl]phosphonic acid	30% inhibition at 0.1 mM	Mycobacterium tuberculosis
[3-[acetyl(hydroxy)amino]-1-(2-methylphenyl)propyl]phosphonic acid	55% inhibition at 0.1 mM	Mycobacterium tuberculosis
[3-[acetyl(hydroxy)amino]-1-[2-(2-hydroxyethyl)phenyl]propyl]phosphonic acid	35% inhibition at 0.1 mM	Mycobacterium tuberculosis
[3-[acetyl(hydroxy)amino]-1-[2-(hydroxymethyl)phenyl]propyl]phosphonic acid	36% inhibition at 0.1 mM	Mycobacterium tuberculosis
[3-[acetyl(hydroxy)amino]-1-[2-(methoxymethyl)phenyl]propyl]phosphonic acid	30% inhibition at 0.1 mM	Mycobacterium tuberculosis
[3-[acetyl(hydroxy)amino]-1-[2-(pyridin-3-yl)phenyl]propyl]phosphonic acid	20% inhibition at 0.1 mM	Mycobacterium tuberculosis
[3-[acetyl(hydroxy)amino]-1-[2-(thiophen-2-yl)phenyl]propyl]phosphonic acid	30% inhibition at 0.1 mM	Mycobacterium tuberculosis

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	required	Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
1-deoxy-D-xylulose 5-phosphate + NADPH + H+	Mycobacterium tuberculosis	-	2-C-methyl-D-erythritol 4-phosphate + NADP+	-	?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+	Mycobacterium tuberculosis H37Rv	-	2-C-methyl-D-erythritol 4-phosphate + NADP+	-	?

Organism

Organism	UniProt	Comment	Textmining
Mycobacterium tuberculosis	P9WNS1	-	-
Mycobacterium tuberculosis H37Rv	P9WNS1	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
1-deoxy-D-xylulose 5-phosphate + NADPH + H+	-	Mycobacterium tuberculosis	2-C-methyl-D-erythritol 4-phosphate + NADP+	-	?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+	-	Mycobacterium tuberculosis H37Rv	2-C-methyl-D-erythritol 4-phosphate + NADP+	-	?

Synonyms

Synonyms	Comment	Organism
1-deoxy-D-xylulose 5-phosphate reductoisomerase	-	Mycobacterium tuberculosis
DXR	-	Mycobacterium tuberculosis

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
22	-	assay at	Mycobacterium tuberculosis

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.5	-	assay at	Mycobacterium tuberculosis

Cofactor

Cofactor	Comment	Organism	Structure
NADPH	-	Mycobacterium tuberculosis

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor
0.00008	-	pH 7.5, 22°C	Mycobacterium tuberculosis	fosmidomycin
0.00015	-	pH 7,5, 22°C	Mycobacterium tuberculosis	3-(N-hydroxyformamido)-1-(3,4-dichlorophenyl)propylphosphonic acid
0.00016	-	pH 7.5, 22°C	Mycobacterium tuberculosis	FR900098
0.0007	-	pH 7,5, 22°C	Mycobacterium tuberculosis	3-(N-hydroxyacetamido)-1-(3,4-dichlorophenyl)propylphosphonic acid
0.0056	-	pH 7,5, 22°C	Mycobacterium tuberculosis	3-(N-hydroxyformamido)-1-(2-bromophenyl)propylphosphonic acid
0.0074	-	pH 7,5, 22°C	Mycobacterium tuberculosis	(3-(N-hydroxyacetamido)-1-phenyl)propylphosphonic acid
0.022	-	pH 7,5, 22°C	Mycobacterium tuberculosis	ethyl hydrogen [3-[acetyl(hydroxy)amino]-1-(3,4-dichlorophenyl)propyl]phosphonate
0.038	-	pH 7,5, 22°C	Mycobacterium tuberculosis	ethyl hydrogen [1-(3,4-dichlorophenyl)-3-[formyl(hydroxy)amino]propyl]phosphonate
0.1	-	above, pH 7,5, 22°C	Mycobacterium tuberculosis	diethyl (1-(3,4-dichlorophenyl)-3-(N-hydroxyformamido)propyl)phosphonate
0.1	-	above, pH 7,5, 22°C	Mycobacterium tuberculosis	diethyl (1-(3,4-dichlorophenyl)-3-(N-hydroxyacetamido)propyl)phosphonate
0.15	-	pH 7,5, 22°C	Mycobacterium tuberculosis	[3-[acetyl(hydroxy)amino]-1-[2-(2-hydroxyethyl)phenyl]propyl]phosphonic acid
0.205	-	pH 7,5, 22°C	Mycobacterium tuberculosis	[3-[acetyl(hydroxy)amino]-1-(2-methylphenyl)propyl]phosphonic acid
0.21	-	pH 7,5, 22°C	Mycobacterium tuberculosis	[3-[acetyl(hydroxy)amino]-1-(2-bromophenyl)propyl]phosphonic acid
0.465	-	pH 7,5, 22°C	Mycobacterium tuberculosis	[3-[acetyl(hydroxy)amino]-1-[2-(hydroxymethyl)phenyl]propyl]phosphonic acid