Literature summary for 1.1.1.169 extracted from

Aikawa, Y.; Nishitani, Y.; Tomita, H.; Atomi, H.; Miki, K.
Crystal structure of archaeal ketopantoate reductase complexed with coenzyme a and 2-oxopantoate provides structural insights into feedback regulation (2016), Proteins, 84, 374-382.

Search for more literature for 1.1.1.169

Cloned(Commentary)

Cloned (Comment)	Organism
gene TK1968, sequence comparisons, recombinant expression of wild-type and mutant enzymes in Escherichia coli strain Rosetta2 (DE3) pLysS	Thermococcus kodakarensis

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified enzyme in complex with CoA and 2-oxopantoate, hanging drop vapor diffusion method, mixing of 0.001 ml of 10 mg/ml protein and 1 mM CoA and 1 mM 2-oxopantoate with 0.001 ml of reservoir solution containing 100 mM Na acetate, pH 4.5, 20-25% v/v 2-methyl-2,4-pentanediol, and equilibration against 0.5 ml of reservoir solution, at 20°C, 3 days, X-ray diffraction structure determination and analysis at 1.65 A resolution, modeling by molecular replacement method using N-terminal (1-165 residues) and C-terminal (171-309 residues) domains of Ec-KPR structure, PDB ID 2OFP, as separated search models, respectively	Thermococcus kodakarensis

Crystallization (Comment)

Organism

purified enzyme in complex with CoA and 2-oxopantoate, hanging drop vapor diffusion method, mixing of 0.001 ml of 10 mg/ml protein and 1 mM CoA and 1 mM 2-oxopantoate with 0.001 ml of reservoir solution containing 100 mM Na acetate, pH 4.5, 20-25% v/v 2-methyl-2,4-pentanediol, and equilibration against 0.5 ml of reservoir solution, at 20°C, 3 days, X-ray diffraction structure determination and analysis at 1.65 A resolution, modeling by molecular replacement method using N-terminal (1-165 residues) and C-terminal (171-309 residues) domains of Ec-KPR structure, PDB ID 2OFP, as separated search models, respectively

Thermococcus kodakarensis

Protein Variants

Protein Variants	Comment	Organism
C84A	site-directed mutagenesis, crystal structure analysis, overview	Thermococcus kodakarensis

Inhibitors

Inhibitors	Comment	Organism	Structure
CoA	feedback inhibition, competitive with NADPH, the binding sites of CoA and NADP+ overlap, explaining the competitive manner of inhibition by CoA, binding structure analysis, overview	Thermococcus kodakarensis

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
(R)-pantoate + NADP+	Thermococcus kodakarensis	-	2-dehydropantoate + NADPH + H+	-	r
(R)-pantoate + NADP+	Thermococcus kodakarensis ATCC BAA-918	-	2-dehydropantoate + NADPH + H+	-	r

Organism

Organism	UniProt	Comment	Textmining
Thermococcus kodakarensis	Q5JGC2	-	-
Thermococcus kodakarensis ATCC BAA-918	Q5JGC2	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant wild-type and mutant enzymes from Escherichia coli strain Rosetta2 (DE3) pLysS by nickel affinity chromatography, avidin affinity chromatography, and dialysis	Thermococcus kodakarensis

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
(R)-pantoate + NADP+	-	Thermococcus kodakarensis	2-dehydropantoate + NADPH + H+	-	r
(R)-pantoate + NADP+	substrate binding structure analysis, overview	Thermococcus kodakarensis	2-dehydropantoate + NADPH + H+	-	r
(R)-pantoate + NADP+	-	Thermococcus kodakarensis ATCC BAA-918	2-dehydropantoate + NADPH + H+	-	r
(R)-pantoate + NADP+	substrate binding structure analysis, overview	Thermococcus kodakarensis ATCC BAA-918	2-dehydropantoate + NADPH + H+	-	r

Subunits

Subunits	Comment	Organism
More	enzyme structure analysis and comparisons, overview	Thermococcus kodakarensis

Synonyms

Synonyms	Comment	Organism
ketopantoate reductase	-	Thermococcus kodakarensis
KPR	-	Thermococcus kodakarensis
Tk-KPR	-	Thermococcus kodakarensis
TK1968	-	Thermococcus kodakarensis

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
70	-	assay at	Thermococcus kodakarensis

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
6.4	-	assay at	Thermococcus kodakarensis

Cofactor

Cofactor	Comment	Organism	Structure
NADP+	the binding sites of CoA and NADP+ overlap, explaining the competitive manner of inhibition by CoA, binding structure analysis, overview	Thermococcus kodakarensis

General Information

General Information	Comment	Organism
additional information	CoA and 2-oxopantoate cooperatively trigger a conformational change from an open form to a closed enzyme form, structure analysis, overview	Thermococcus kodakarensis
physiological function	ketopantoate reductase (KPR) catalyzes the NAD(P)H-dependent reduction of 2-oxopantoate to pantoate, and is a target of the feedback inhibition by CoA in archaea. Coenzyme A (CoA) plays essential roles in a variety of metabolic pathways in all three domains of life. The biosynthesis pathway of CoA is strictly regulated by feedback inhibition. In bacteria and eukaryotes, pantothenate kinase is the target of feedback inhibition by CoA	Thermococcus kodakarensis