Literature summary for 1.1.1.42 extracted from

Avellaneda Matteo, D.; Grunseth, A.J.; Gonzalez, E.R.; Anselmo, S.L.; Kennedy, M.A.; Moman, P.; Scott, D.A.; Hoang, A.; Sohl, C.D.
Molecular mechanisms of isocitrate dehydrogenase 1 (IDH1) mutations identified in tumors The role of size and hydrophobicity at residue 132 on catalytic efficiency (2017), J. Biol. Chem., 292, 7971-7983 .

Cloned(Commentary)

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

Protein Variants

Protein Variants	Comment	Organism
A134D	the mutant shows severely reduced catalytic efficiency compared to the wild type enzyme	Homo sapiens
H133Q	the mutant shows strongly reduced catalytic efficiency compared to the wild type enzyme	Homo sapiens
R100Q	the mutant shows severely reduced catalytic efficiency compared to the wild type enzyme	Homo sapiens
R132A	the mutant shows severely reduced catalytic efficiency compared to the wild type enzyme	Homo sapiens
R132C	the mutant shows severely reduced catalytic efficiency compared to the wild type enzyme	Homo sapiens
R132G	the mutant shows severely reduced catalytic efficiency compared to the wild type enzyme	Homo sapiens
R132H	the mutant shows severely reduced catalytic efficiency compared to the wild type enzyme	Homo sapiens
R132K	the mutant shows severely reduced catalytic efficiency compared to the wild type enzyme	Homo sapiens
R132N	the mutant shows severely reduced catalytic efficiency compared to the wild type enzyme	Homo sapiens
R132Q	the mutant shows severely reduced catalytic efficiency compared to the wild type enzyme	Homo sapiens
R132W	the mutant shows severely reduced catalytic efficiency compared to the wild type enzyme	Homo sapiens

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism
0.0025	-	NADPH	Km less than 0.0025 mM or equal, mutant enzyme R100Q, at pH 7.5 and 21°C	Homo sapiens
0.005	-	NADPH	Km less than 0.005 mM or equal, mutant enzyme R132H, at pH 7.5 and 21°C	Homo sapiens
0.005	-	NADPH	mutant enzyme R100Q, at pH 7.5 and 37°C	Homo sapiens
0.01	-	NADPH	Km less than 0.01 mM or equal, wild type enzyme, at pH 7.5 and 37°C	Homo sapiens
0.01	-	NADPH	mutant enzyme R132C, at pH 7.5 and 37°C	Homo sapiens
0.015	-	isocitrate	wild type enzyme, at pH 7.5 and 21°C	Homo sapiens
0.025	-	NADPH	Km less than 0.025 mM or equal, mutant enzyme R132C, at pH 7.5 and 21°C	Homo sapiens
0.025	-	NADPH	Km less than 0.025 mM or equal, mutant enzyme R132G, at pH 7.5 and 21°C	Homo sapiens
0.025	-	NADPH	Km less than 0.025 mM or equal, mutant enzyme R132H, at pH 7.5 and 37°C	Homo sapiens
0.025	-	NADPH	Km less than 0.025 mM, mutant enzyme R132G, at pH 7.5 and 37°C	Homo sapiens
0.03	-	NADP+	wild type enzyme, at pH 7.5 and 21°C	Homo sapiens
0.067	-	NADP+	mutant enzyme R132G, at pH 7.5 and 37°C	Homo sapiens
0.07	-	NADP+	mutant enzyme R100Q, at pH 7.5 and 21°C	Homo sapiens
0.08	-	NADP+	wild type enzyme, at pH 7.5 and 37°C	Homo sapiens
0.101	-	NADP+	mutant enzyme H133Q, at pH 7.5 and 21°C	Homo sapiens
0.11	-	2-oxoglutarate	mutant enzyme R132A, at pH 7.5 and 37°C	Homo sapiens
0.14	-	NADP+	mutant enzyme R132G, at pH 7.5 and 21°C	Homo sapiens
0.16	-	NADP+	mutant enzyme H133Q, at pH 7.5 and 37°C	Homo sapiens
0.18	-	NADP+	mutant enzyme R100Q, at pH 7.5 and 37°C	Homo sapiens
0.22	-	isocitrate	wild type enzyme, at pH 7.5 and 37°C	Homo sapiens
0.26	-	2-oxoglutarate	mutant enzyme R132Q, at pH 7.5 and 37°C	Homo sapiens
0.28	-	isocitrate	mutant enzyme H133Q, at pH 7.5 and 21°C	Homo sapiens
0.3	-	2-oxoglutarate	mutant enzyme R132G, at pH 7.5 and 21°C	Homo sapiens
0.34	-	2-oxoglutarate	mutant enzyme R132G, at pH 7.5 and 37°C	Homo sapiens
0.36	-	2-oxoglutarate	mutant enzyme R132C, at pH 7.5 and 21°C	Homo sapiens
0.36	-	2-oxoglutarate	mutant enzyme R132C, at pH 7.5 and 37°C	Homo sapiens
0.4	-	isocitrate	mutant enzyme H133Q, at pH 7.5 and 37°C	Homo sapiens
0.5	-	2-oxoglutarate	wild type enzyme, at pH 7.5 and 37°C	Homo sapiens
0.58	-	NADP+	mutant enzyme R132C, at pH 7.5 and 21°C	Homo sapiens
0.61	-	2-oxoglutarate	mutant enzyme R132K, at pH 7.5 and 37°C	Homo sapiens
0.7	-	NADP+	mutant enzyme A134D, at pH 7.5 and 21°C	Homo sapiens
0.75	-	NADP+	mutant enzyme R132C, at pH 7.5 and 37°C	Homo sapiens
0.8	-	isocitrate	mutant enzyme R132Q, at pH 7.5 and 37°C	Homo sapiens
0.82	-	2-oxoglutarate	mutant enzyme R132W, at pH 7.5 and 37°C	Homo sapiens
1	-	NADP+	mutant enzyme R132H, at pH 7.5 and 21°C	Homo sapiens
1.1	-	2-oxoglutarate	mutant enzyme R132H, at pH 7.5 and 37°C	Homo sapiens
1.1	-	isocitrate	mutant enzyme R132K, at pH 7.5 and 37°C	Homo sapiens
1.2	-	NADP+	mutant enzyme A134D, at pH 7.5 and 37°C	Homo sapiens
1.5	-	isocitrate	mutant enzyme R132N, at pH 7.5 and 37°C	Homo sapiens
1.6	-	NADP+	mutant enzyme R132H, at pH 7.5 and 37°C	Homo sapiens
1.8	-	2-oxoglutarate	mutant enzyme R132H, at pH 7.5 and 21°C	Homo sapiens
2.7	-	isocitrate	mutant enzyme A134D, at pH 7.5 and 21°C	Homo sapiens
3.6	-	isocitrate	mutant enzyme R132G, at pH 7.5 and 21°C	Homo sapiens
3.6	-	isocitrate	mutant enzyme R132W, at pH 7.5 and 37°C	Homo sapiens
4.2	-	isocitrate	mutant enzyme R132H, at pH 7.5 and 37°C	Homo sapiens
5.3	-	isocitrate	mutant enzyme R132C, at pH 7.5 and 21°C	Homo sapiens
5.7	-	isocitrate	mutant enzyme R132A, at pH 7.5 and 37°C	Homo sapiens
6	-	isocitrate	mutant enzyme R132H, at pH 7.5 and 21°C	Homo sapiens
7	-	isocitrate	mutant enzyme R132G, at pH 7.5 and 37°C	Homo sapiens
8	-	isocitrate	mutant enzyme A134D, at pH 7.5 and 37°C	Homo sapiens
8	-	isocitrate	mutant enzyme R100Q, at pH 7.5 and 37°C	Homo sapiens
8.2	-	isocitrate	mutant enzyme R132C, at pH 7.5 and 37°C	Homo sapiens
9	-	isocitrate	mutant enzyme R100Q, at pH 7.5 and 21°C	Homo sapiens
10	-	2-oxoglutarate	mutant enzyme R100Q, at pH 7.5 and 21°C	Homo sapiens
10	-	2-oxoglutarate	mutant enzyme R132N, at pH 7.5 and 37°C	Homo sapiens
12	-	2-oxoglutarate	mutant enzyme R100Q, at pH 7.5 and 37°C	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
cytosol	-	Homo sapiens	5829	-
peroxisome	-	Homo sapiens	5777	-

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	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.
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

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
2-oxoglutarate + NADPH + H+	the reaction is catalyzed by diverse R132 mutant enzymes	Homo sapiens	D-2-hydroxyglutarate + NADP+	-	r
isocitrate + NADP+	-	Homo sapiens	2-oxoglutarate + CO2 + NADPH + H+	-	r

Synonyms

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

Temperature Stability [°C]

Temperature Stability Minimum [°C]	Temperature Stability Maximum [°C]	Comment	Organism
49.1	-	melting temperature	Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s]	Turnover Number Maximum [1/s]	Substrate	Comment	Organism
0.016	-	2-oxoglutarate	kcat less than 0.016 s-1 or equal, mutant enzyme H133Q, at pH 7.5 and 37°C	Homo sapiens
0.017	-	2-oxoglutarate	wild type enzyme, at pH 7.5 and 21°C	Homo sapiens
0.019	-	2-oxoglutarate	wild type enzyme, at pH 7.5 and 37°C	Homo sapiens
0.019	-	2-oxoglutarate	kcat less than 0.019 s-1 or equal, mutant enzyme A134D, at pH 7.5 and 37°C	Homo sapiens
0.02	-	2-oxoglutarate	mutant enzyme A134D, at pH 7.5 and 21°C	Homo sapiens
0.034	-	2-oxoglutarate	mutant enzyme H133, at pH 7.5 and 21°C	Homo sapiens
0.047	-	isocitrate	mutant enzyme R132N, at pH 7.5 and 37°C	Homo sapiens
0.12	-	isocitrate	mutant enzyme R132H, at pH 7.5 and 21°C	Homo sapiens
0.128	-	2-oxoglutarate	mutant enzyme R100Q, at pH 7.5 and 21°C	Homo sapiens
0.2	-	isocitrate	mutant enzyme A134D, at pH 7.5 and 21°C	Homo sapiens
0.34	-	2-oxoglutarate	mutant enzyme R100Q, at pH 7.5 and 37°C	Homo sapiens
0.37	-	2-oxoglutarate	mutant enzyme R132A, at pH 7.5 and 37°C	Homo sapiens
0.43	-	2-oxoglutarate	mutant enzyme R132H, at pH 7.5 and 21°C	Homo sapiens
0.45	-	2-oxoglutarate	mutant enzyme R132G, at pH 7.5 and 21°C	Homo sapiens
0.54	-	2-oxoglutarate	mutant enzyme R132W, at pH 7.5 and 37°C	Homo sapiens
0.57	-	2-oxoglutarate	mutant enzyme R132K, at pH 7.5 and 37°C	Homo sapiens
0.79	-	2-oxoglutarate	mutant enzyme R132N, at pH 7.5 and 37°C	Homo sapiens
0.84	-	2-oxoglutarate	mutant enzyme R132C, at pH 7.5 and 21°C	Homo sapiens
1	-	isocitrate	mutant enzyme R132G, at pH 7.5 and 21°C	Homo sapiens
1.21	-	isocitrate	mutant enzyme R132W, at pH 7.5 and 37°C	Homo sapiens
1.4	-	isocitrate	mutant enzyme R100Q, at pH 7.5 and 21°C	Homo sapiens
1.59	-	2-oxoglutarate	mutant enzyme R132G, at pH 7.5 and 37°C	Homo sapiens
1.6	-	2-oxoglutarate	mutant enzyme R132C, at pH 7.5 and 37°C	Homo sapiens
1.61	-	isocitrate	mutant enzyme R132C, at pH 7.5 and 21°C	Homo sapiens
2.3	-	isocitrate	mutant enzyme A134D, at pH 7.5 and 37°C	Homo sapiens
2.4	-	isocitrate	mutant enzyme R132H, at pH 7.5 and 37°C	Homo sapiens
4.2	-	2-oxoglutarate	mutant enzyme R132H, at pH 7.5 and 37°C	Homo sapiens
4.4	-	isocitrate	mutant enzyme R132C, at pH 7.5 and 37°C	Homo sapiens
4.7	-	2-oxoglutarate	mutant enzyme R132Q, at pH 7.5 and 37°C	Homo sapiens
5.6	-	isocitrate	mutant enzyme R100Q, at pH 7.5 and 37°C	Homo sapiens
7.2	-	isocitrate	mutant enzyme R132K, at pH 7.5 and 37°C	Homo sapiens
9.2	-	isocitrate	mutant enzyme R132Q, at pH 7.5 and 37°C	Homo sapiens
9.3	-	isocitrate	mutant enzyme R132G, at pH 7.5 and 37°C	Homo sapiens
9.4	-	isocitrate	mutant enzyme H133Q, at pH 7.5 and 21°C	Homo sapiens
10.4	-	isocitrate	mutant enzyme R132A, at pH 7.5 and 37°C	Homo sapiens
11	-	isocitrate	wild type enzyme, at pH 7.5 and 21°C	Homo sapiens
45	-	isocitrate	mutant enzyme H133Q, at pH 7.5 and 37°C	Homo sapiens
85	-	isocitrate	wild type enzyme, 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
0.013	-	2-oxoglutarate	mutant enzyme R100Q, at pH 7.5 and 21°C	Homo sapiens
0.02	-	isocitrate	mutant enzyme R132H, at pH 7.5 and 21°C	Homo sapiens
0.028	-	2-oxoglutarate	mutant enzyme R100Q, at pH 7.5 and 37°C	Homo sapiens
0.031	-	isocitrate	mutant enzyme R132N, at pH 7.5 and 37°C	Homo sapiens
0.04	-	2-oxoglutarate	wild type enzyme, at pH 7.5 and 37°C	Homo sapiens
0.074	-	isocitrate	mutant enzyme A134D, at pH 7.5 and 21°C	Homo sapiens
0.08	-	2-oxoglutarate	mutant enzyme R132N, at pH 7.5 and 37°C	Homo sapiens
0.16	-	isocitrate	mutant enzyme R100Q, at pH 7.5 and 21°C	Homo sapiens
0.24	-	2-oxoglutarate	mutant enzyme R132H, at pH 7.5 and 21°C	Homo sapiens
0.28	-	isocitrate	mutant enzyme R132G, at pH 7.5 and 21°C	Homo sapiens
0.29	-	isocitrate	mutant enzyme A134D, at pH 7.5 and 37°C	Homo sapiens
0.3	-	isocitrate	mutant enzyme R132C, at pH 7.5 and 21°C	Homo sapiens
0.34	-	isocitrate	mutant enzyme R132W, at pH 7.5 and 37°C	Homo sapiens
0.54	-	isocitrate	mutant enzyme R132C, at pH 7.5 and 37°C	Homo sapiens
0.57	-	isocitrate	mutant enzyme R132H, at pH 7.5 and 37°C	Homo sapiens
0.659	-	2-oxoglutarate	mutant enzyme R132W, at pH 7.5 and 37°C	Homo sapiens
0.7	-	isocitrate	mutant enzyme R100Q, at pH 7.5 and 37°C	Homo sapiens
0.9	-	2-oxoglutarate	mutant enzyme R132K, at pH 7.5 and 37°C	Homo sapiens
1.3	-	isocitrate	mutant enzyme R132G, at pH 7.5 and 37°C	Homo sapiens
1.5	-	2-oxoglutarate	mutant enzyme R132G, at pH 7.5 and 21°C	Homo sapiens
1.8	-	isocitrate	mutant enzyme R132A, at pH 7.5 and 37°C	Homo sapiens
2.3	-	2-oxoglutarate	mutant enzyme R132C, at pH 7.5 and 21°C	Homo sapiens
3.4	-	2-oxoglutarate	mutant enzyme R132A, at pH 7.5 and 37°C	Homo sapiens
3.8	-	2-oxoglutarate	mutant enzyme R132H, at pH 7.5 and 37°C	Homo sapiens
4.4	-	2-oxoglutarate	mutant enzyme R132C, at pH 7.5 and 37°C	Homo sapiens
5	-	2-oxoglutarate	mutant enzyme R132G, at pH 7.5 and 37°C	Homo sapiens
7	-	isocitrate	mutant enzyme R132K, at pH 7.5 and 37°C	Homo sapiens
12	-	isocitrate	mutant enzyme R132Q, at pH 7.5 and 37°C	Homo sapiens
18	-	2-oxoglutarate	mutant enzyme R132Q, at pH 7.5 and 37°C	Homo sapiens
35	-	isocitrate	mutant enzyme H133Q, at pH 7.5 and 21°C	Homo sapiens
110	-	isocitrate	mutant enzyme H133Q, at pH 7.5 and 37°C	Homo sapiens
390	-	isocitrate	wild type enzyme, at pH 7.5 and 37°C	Homo sapiens
730	-	isocitrate	wild type enzyme, at pH 7.5 and 21°C	Homo sapiens