Literature summary for 1.1.1.42 extracted from

Luna, L.A.; Lesecq, Z.; White, K.A.; Hoang, A.; Scott, D.A.; Zagnitko, O.; Bobkov, A.A.; Barber, D.L.; Schiffer, J.M.; Isom, D.G.; Sohl, C.D.
An acidic residue buried in the dimer interface of isocitrate dehydrogenase 1 (IDH1) helps regulate catalysis and pH sensitivity (2020), Biochem. J., 477, 2999-3018 .

Cloned(Commentary)

Cloned (Comment)	Organism
expressed in Escherichia coli BL21-Gold (DE3) cells	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
D273L	the mutant exhibits an about 170fold decrease in catalytic efficiency, driven by a 5.4fold decrease in kcat and 31fold increase in Km as compared to the wild type enzyme	Homo sapiens
D273L/R132H	catalytically inactive	Homo sapiens
D273N	the mutant has a more than 500fold decrease in kcat/Km, driven primarily through more than 300fold increase in Km as compared to the wild type enzyme	Homo sapiens
D273N/R132H	catalytically inactive	Homo sapiens
D273S	the mutant exhibits adecrease in catalytic efficiency, driven by a 2.5fold decrease in kcat and 200fold increase in Km as compared to the wild type enzyme	Homo sapiens
D273S/R132H	catalytically inactive	Homo sapiens
K217M	the mutant shows reduced catalytic efficiency as compared to the wild type enzym	Homo sapiens
K217Q	the mutant shows reduced catalytic efficiency as compared to the wild type enzym	Homo sapiens
R132H	the mutant catalyzes the conversion of 2-oxoglutarate plus NADPH to D-2-hydroxyglutarate	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
AGI-5198	-	Homo sapiens
ML309	-	Homo sapiens

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism
0.027	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 6.2 and 37°C	Homo sapiens
0.03	-	isocitrate	wild type enzyme, in Tris buffer, at pH 7.5 and 37°C	Homo sapiens
0.034	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 6.5 and 37°C	Homo sapiens
0.035	-	isocitrate	wild type enzyme, in Tris buffer, at pH 7.8 and 37°C	Homo sapiens
0.038	-	isocitrate	wild type enzyme, in Tris buffer, at pH 8.0 and 37°C	Homo sapiens
0.04	-	2-oxoglutarate	wild type enzyme, in Bis-Tris buffer, at pH 6.2 and 37°C	Homo sapiens
0.04	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 6.8 and 37°C	Homo sapiens
0.042	-	isocitrate	wild type enzyme, in Bis-Tris buffer, at pH 6.2 and 37°C	Homo sapiens
0.048	-	isocitrate	wild type enzyme, in Bis-Tris buffer, at pH 6.5 and 37°C	Homo sapiens
0.05	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 7.0 and 37°C	Homo sapiens
0.06	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 7.2 and 37°C	Homo sapiens
0.061	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens
0.066	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 7.8 and 37°C	Homo sapiens
0.067	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 8.0 and 37°C	Homo sapiens
0.075	-	isocitrate	wild type enzyme, in Bis-Tris buffer, at pH 7.0 and 37°C	Homo sapiens
0.11	-	isocitrate	wild type enzyme, in Tris buffer, at pH 7.2 and 37°C	Homo sapiens
0.12	-	2-oxoglutarate	wild type enzyme, in Bis-Tris buffer, at pH 6.5 and 37°C	Homo sapiens
0.14	-	2-oxoglutarate	wild type enzyme, in Bis-Tris buffer, at pH 6.8 and 37°C	Homo sapiens
0.15	-	isocitrate	mutant enzyme K217M, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens
0.246	-	2-oxoglutarate	wild type enzyme, in Tris buffer, at pH 7.5 and 37°C	Homo sapiens
0.25	-	isocitrate	mutant enzyme K217Q, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens
0.26	-	2-oxoglutarate	wild type enzyme, in Bis-Tris buffer, at pH 7.0 and 37°C	Homo sapiens
0.26	-	2-oxoglutarate	wild type enzyme, in Tris buffer, at pH 7.2 and 37°C	Homo sapiens
0.28	-	2-oxoglutarate	wild type enzyme, in potassium phosphate buffer, at pH 7.2 and 37°C	Homo sapiens
0.46	-	2-oxoglutarate	wild type enzyme, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens
0.6	-	2-oxoglutarate	wild type enzyme, in potassium phosphate buffer, at pH 6.2 and 37°C	Homo sapiens
0.65	-	2-oxoglutarate	wild type enzyme, in potassium phosphate buffer, at pH 6.8 and 37°C	Homo sapiens
0.71	-	2-oxoglutarate	wild type enzyme, in potassium phosphate buffer, at pH 7.0 and 37°C	Homo sapiens
0.87	-	2-oxoglutarate	wild type enzyme, in potassium phosphate buffer, at pH 7.8 and 37°C	Homo sapiens
1	-	2-oxoglutarate	wild type enzyme, in potassium phosphate buffer, at pH 6.5 and 37°C	Homo sapiens
1.5	-	2-oxoglutarate	mutant enzyme R132H, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens
1.9	-	isocitrate	mutant enzyme D273L, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens
12	-	isocitrate	mutant enzyme D273S, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens
19	-	isocitrate	mutant enzyme D273N, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	required for catalysis, 10 mM used in assay conditions	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
2-oxoglutarate + CO2 + NADPH + H+	Homo sapiens	-	isocitrate + NADP+	-	r
isocitrate + NADP+	Homo sapiens	-	2-oxoglutarate + CO2 + NADPH + H+	-	r

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	O75874	-	-

Purification (Commentary)

Purification (Comment)	Organism
Ni-NTA column chromatography	Homo sapiens

Source Tissue

Source Tissue	Comment	Organism	Textmining
HT-1080 cell	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
2-oxoglutarate + CO2 + NADPH + H+	-	Homo sapiens	isocitrate + NADP+	-	r
2-oxoglutarate + NADPH + H+	the reaction is catalyzed by mutant enzyme R132H	Homo sapiens	D-2-hydroxyglutarate + NADP+	-	r
isocitrate + NADP+	-	Homo sapiens	2-oxoglutarate + CO2 + NADPH + H+	-	r

Subunits

Subunits	Comment	Organism
homodimer	-	Homo sapiens

Synonyms

Synonyms	Comment	Organism
IDH1	-	Homo sapiens
isocitrate dehydrogenase 1	-	Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s]	Turnover Number Maximum [1/s]	Substrate	Comment	Organism
1.44	-	2-oxoglutarate	mutant enzyme R132H, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens
1.6	-	2-oxoglutarate	wild type enzyme, in Bis-Tris buffer, at pH 6.2 and 37°C	Homo sapiens
1.87	-	2-oxoglutarate	wild type enzyme, in potassium phosphate buffer, at pH 7.8 and 37°C	Homo sapiens
3.2	-	2-oxoglutarate	wild type enzyme, in Bis-Tris buffer, at pH 6.5 and 37°C	Homo sapiens
3.3	-	2-oxoglutarate	wild type enzyme, in Bis-Tris buffer, at pH 6.8 and 37°C	Homo sapiens
3.4	-	2-oxoglutarate	wild type enzyme, in Tris buffer, at pH 7.2 and 37°C	Homo sapiens
3.5	-	2-oxoglutarate	wild type enzyme, in potassium phosphate buffer, at pH 6.2 and 37°C	Homo sapiens
3.6	-	2-oxoglutarate	wild type enzyme, in Tris buffer, at pH 7.5 and 37°C	Homo sapiens
3.8	-	2-oxoglutarate	wild type enzyme, in Bis-Tris buffer, at pH 7.0 and 37°C	Homo sapiens
3.8	-	2-oxoglutarate	wild type enzyme, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens
3.87	-	2-oxoglutarate	wild type enzyme, in potassium phosphate buffer, at pH 7.2 and 37°C	Homo sapiens
4.1	-	2-oxoglutarate	wild type enzyme, in potassium phosphate buffer, at pH 6.5 and 37°C	Homo sapiens
4.1	-	2-oxoglutarate	wild type enzyme, in potassium phosphate buffer, at pH 7.0 and 37°C	Homo sapiens
4.9	-	2-oxoglutarate	wild type enzyme, in potassium phosphate buffer, at pH 6.8 and 37°C	Homo sapiens
7	-	isocitrate	mutant enzyme D273L, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens
15	-	isocitrate	mutant enzyme D273S, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens
20	-	isocitrate	wild type enzyme, in Bis-Tris buffer, at pH 6.2 and 37°C	Homo sapiens
20.2	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 6.2 and 37°C	Homo sapiens
22	-	isocitrate	mutant enzyme D273N, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens
23	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 6.5 and 37°C	Homo sapiens
23.1	-	isocitrate	wild type enzyme, in Bis-Tris buffer, at pH 6.5 and 37°C	Homo sapiens
27.5	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 6.8 and 37°C	Homo sapiens
28.7	-	isocitrate	mutant enzyme K217Q, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens
31.7	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 7.0 and 37°C	Homo sapiens
32	-	isocitrate	wild type enzyme, in Bis-Tris buffer, at pH 7.0 and 37°C	Homo sapiens
35.4	-	isocitrate	wild type enzyme, in Tris buffer, at pH 7.8 and 37°C	Homo sapiens
35.5	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 7.2 and 37°C	Homo sapiens
37.6	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens
38.3	-	isocitrate	wild type enzyme, in Tris buffer, at pH 8.0 and 37°C	Homo sapiens
39	-	isocitrate	wild type enzyme, in Tris buffer, at pH 7.2 and 37°C	Homo sapiens
39.2	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 8.0 and 37°C	Homo sapiens
40	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 7.8 and 37°C	Homo sapiens
40.4	-	isocitrate	wild type enzyme, in Tris buffer, at pH 7.5 and 37°C	Homo sapiens
42	-	isocitrate	mutant enzyme K217M, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens

Cofactor

Cofactor	Comment	Organism	Structure
NADP+	-	Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs^-1]	kcat/KM Value Maximum [1/mMs^-1]	Substrate	Comment	Organism
1	-	2-oxoglutarate	mutant enzyme R132H, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens
1.2	-	isocitrate	mutant enzyme D273N, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens
1.3	-	isocitrate	mutant enzyme D273S, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens
2.1	-	2-oxoglutarate	wild type enzyme, in potassium phosphate buffer, at pH 7.8 and 37°C	Homo sapiens
3.7	-	isocitrate	mutant enzyme D273L, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens
4.1	-	2-oxoglutarate	wild type enzyme, in potassium phosphate buffer, at pH 6.5 and 37°C	Homo sapiens
5.8	-	2-oxoglutarate	wild type enzyme, in potassium phosphate buffer, at pH 7.0 and 37°C	Homo sapiens
6	-	2-oxoglutarate	wild type enzyme, in potassium phosphate buffer, at pH 6.2 and 37°C	Homo sapiens
7.5	-	2-oxoglutarate	wild type enzyme, in potassium phosphate buffer, at pH 6.8 and 37°C	Homo sapiens
8.3	-	2-oxoglutarate	wild type enzyme, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens
13	-	2-oxoglutarate	wild type enzyme, in Tris buffer, at pH 7.2 and 37°C	Homo sapiens
14	-	2-oxoglutarate	wild type enzyme, in potassium phosphate buffer, at pH 7.2 and 37°C	Homo sapiens
15	-	2-oxoglutarate	wild type enzyme, in Tris buffer, at pH 7.5 and 37°C	Homo sapiens
24	-	2-oxoglutarate	wild type enzyme, in Bis-Tris buffer, at pH 6.8 and 37°C	Homo sapiens
27	-	2-oxoglutarate	wild type enzyme, in Bis-Tris buffer, at pH 6.5 and 37°C	Homo sapiens
27	-	2-oxoglutarate	wild type enzyme, in Bis-Tris buffer, at pH 7.0 and 37°C	Homo sapiens
40	-	2-oxoglutarate	wild type enzyme, in Bis-Tris buffer, at pH 6.2 and 37°C	Homo sapiens
115	-	isocitrate	mutant enzyme K217Q, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens
280	-	isocitrate	mutant enzyme K217M, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens
350	-	isocitrate	wild type enzyme, in Tris buffer, at pH 7.2 and 37°C	Homo sapiens
430	-	isocitrate	wild type enzyme, in Bis-Tris buffer, at pH 7.0 and 37°C	Homo sapiens
480	-	isocitrate	wild type enzyme, in Bis-Tris buffer, at pH 6.2 and 37°C	Homo sapiens
480	-	isocitrate	wild type enzyme, in Bis-Tris buffer, at pH 6.5 and 37°C	Homo sapiens
590	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 7.2 and 37°C	Homo sapiens
590	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 8.0 and 37°C	Homo sapiens
610	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 7.8 and 37°C	Homo sapiens
620	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 7.5 and 37°C	Homo sapiens
630	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 7.0 and 37°C	Homo sapiens
680	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 6.5 and 37°C	Homo sapiens
690	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 6.8 and 37°C	Homo sapiens
750	-	isocitrate	wild type enzyme, in potassium phosphate buffer, at pH 6.2 and 37°C	Homo sapiens
1000	-	isocitrate	wild type enzyme, in Tris buffer, at pH 8.0 and 37°C	Homo sapiens
1010	-	isocitrate	wild type enzyme, in Tris buffer, at pH 7.8 and 37°C	Homo sapiens
1400	-	isocitrate	wild type enzyme, in Tris buffer, at pH 7.5 and 37°C	Homo sapiens