Literature summary for 2.7.8.B13 extracted from

Morii, H.; Okauchi, T.; Nomiya, H.; Ogawa, M.; Fukuda, K.; Taniguchi, H.
Studies of inositol 1-phosphate analogues as inhibitors of the phosphatidylinositol phosphate synthase in mycobacteria (2013), J. Biochem., 153, 257-266.

Search for more literature for 2.7.8.B13

Application

Application	Comment	Organism
drug development	the enzyme is a promising target for the development of anti-mycobacterium drugs	Mycobacterium tuberculosis

Inhibitors

Inhibitors	Comment	Organism	Structure
(+-)-1-deoxy-1-phosphonomethyl-myo-inositol	Ino-C-P, competitive inhibition, 24% and 76% inhibition at 1 mM and 5 mM, respectively	Mycobacterium tuberculosis
(+-)-1-deoxy-1-phosphonomethyl-myo-inositol	leads to growth inhibition	Mycolicibacterium smegmatis
(+-)-1-deoxy-1-[(diethoxyphosphinyl)methyl]-myo-inositol	Ino-C-P(OEt)2, 11% and 40% inhibition at 1 mM and 5 mM, respectively	Mycobacterium tuberculosis
(+-)-1-deoxy-1-[(diethoxyphosphinyl)methyl]-myo-inositol	Ino-C-P(OEt)2, leads to growth inhibition	Mycolicibacterium smegmatis
(+-)-1-O-sulfamoyl-myo-inositol	16% and 45% inhibition at 1 mM and 5 mM, respectively	Mycobacterium tuberculosis
1D-myo-inositol 1-monophosphate	4% and 45% inhibition at 1 mM and 5 mM, respectively	Mycobacterium tuberculosis
1L-1-deoxy-1-carboxymethyl-chiro-inositol	7% and 41% inhibition at 1 mM and 5 mM, respectively	Mycobacterium tuberculosis
1L-1-deoxy-1-carboxymethyl-myo-inositol	7% and 41% inhibition at 1 mM and 5 mM, respectively	Mycobacterium tuberculosis
additional information	chemical synthesis of four types of inositol 1-phosphate derivatives, all synthesized compounds inhibit PIP synthase activity. The phosphonate analogue of inositol 1-phosphate has the greatest inhibitory effect among the synthesized compounds examined, kinetic analysis. No substrate inhibition by 1L-myo-inositol 1-phosphate	Mycobacterium tuberculosis
additional information	no growth inhibition by (+-)-1-O-sulfamoyl-myo-inositol, 1L-1-deoxy-1-carboxymethyl-myo-inositol, and 1 L-1-deoxy-1-carboxymethyl-chiro-inositol	Mycolicibacterium smegmatis
myo-inositol 2-monophosphate	10% and 44% inhibition at 1 mM and 5 mM, respectively	Mycobacterium tuberculosis

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	the enzyme requires Mg2+ or Mn2+	Mycolicibacterium smegmatis
Mg2+	the enzyme requires Mg2+ or Mn2+	Mycobacterium tuberculosis
Mn2+	the enzyme requires Mg2+ or Mn2+	Mycolicibacterium smegmatis
Mn2+	the enzyme requires Mg2+ or Mn2+	Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
CDP-diacylglycerol + 1L-myo-inositol 1-phosphate	Mycolicibacterium smegmatis	-	CMP + 1-phosphatidyl-1D-myo-inositol 3-phosphate	-	?
CDP-diacylglycerol + 1L-myo-inositol 1-phosphate	Mycobacterium tuberculosis	-	CMP + 1-phosphatidyl-1D-myo-inositol 3-phosphate	-	?

Organism

Organism	UniProt	Comment	Textmining
Mycobacterium tuberculosis	-	-	-
Mycolicibacterium smegmatis	-	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
CDP-diacylglycerol + 1L-myo-inositol 1-phosphate	-	Mycolicibacterium smegmatis	CMP + 1-phosphatidyl-1D-myo-inositol 3-phosphate	-	?
CDP-diacylglycerol + 1L-myo-inositol 1-phosphate	-	Mycobacterium tuberculosis	CMP + 1-phosphatidyl-1D-myo-inositol 3-phosphate	-	?

Synonyms

Synonyms	Comment	Organism
phosphatidylinositol phosphate synthase	-	Mycolicibacterium smegmatis
phosphatidylinositol phosphate synthase	-	Mycobacterium tuberculosis
PIP synthase	-	Mycolicibacterium smegmatis
PIP synthase	-	Mycobacterium tuberculosis

Temperature Optimum [°C]

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

pH Optimum

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

General Information

General Information	Comment	Organism
metabolism	distinct pathway for the biosynthesis of phosphatidylinositol in mycobacteria via phosphatidylinositol phosphate (PIP) and phosphatidylinositol phosphate synthase activity	Mycolicibacterium smegmatis
metabolism	distinct pathway for the biosynthesis of phosphatidylinositol in mycobacteria via phosphatidylinositol phosphate (PIP) and phosphatidylinositol phosphate synthase activity	Mycobacterium tuberculosis

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Release 2023.1 (January 2023)