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Literature summary for 1.14.99.66 extracted from

  • Burg, J.M.; Gonzalez, J.J.; Maksimchuk, K.R.; McCafferty, D.G.
    Lysine-specific demethylase 1A (KDM1A/LSD1) product recognition and kinetic analysis of full-length histones (2016), Biochemistry, 55, 1652-1662 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 1.14.99.66

Activating Compound

Activating Compound Comment Organism Structure
CoREST i.e. REST corepressor 1, regulates LSD1 activity towards nucleosomes. CoREST does not alter the catalytic efficiency toward minimal peptide substrat Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
gene KDM1A, codon optimized, recombinant expression of the enzyme LSD1, residues 151-852, in Escherichia coli Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
histone H3 full-length histone H3, which lacks any posttranslational modifications, is a tight-binding, competitive inhibitor; full-length histone H3, which lacks any posttranslational modifications, is a tight-binding, competitive inhibitor of KDM1A demethylation activity with a Ki of 18.9 nM, a value that is approximately 100fold higher than that of the 21-mer peptide of H3. The relative H3 affinity is independent of preincubation time, suggesting that H3 rapidly reaches equilibrium with KDM1A, tight-binding nature of the H3/KDM1A interaction, kinetics, overview. No other core histones exhibits inhibition of KDM1A demethylation activity, which is consistent with H3 being the preferred histone substrate of KDM1A versus H2A, H2B, and H4. Inhibition profiling of full-length histone H3 against KDM1A Homo sapiens
histone H3 1-21 peptide 21-mer H3-derived peptide Homo sapiens
histone H3-1-21 peptide corresponding to the first 21 amino acids of the N-terminal tail of histone H3, competitive inhibitor Homo sapiens
additional information besides histone H3, no other core histones exhibit inhibition of KDM1A demethylation activity; KDM1A tolerance for 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS) at 0.01% w/v and dimethyl sulfoxide (DMSO) at 10% v/v Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
 additional information Michaelis-Menten steady-state kinetics of N-terminally truncated KDM1A and differential KDM1A/CoREST complexes using an H3K4me2 1-21 peptide substrate Homo sapiens
0.00446
-
 [histone H3]-N6,N6-L-dimethyllysine4-1-21 recombinant enzyme, pH 7.5, 25°C Homo sapiens
0.00446
-
 H3K4me2 1-21 peptide pH 7.5, 25°C, recombinant N-terminally truncated KDM1A Homo sapiens
0.00814
-
 H3K4me2 1-21 peptide pH 7.5, 25°C, recombinant N-terminally truncated KDM1A-CoREST-C complex Homo sapiens
0.00814
-
 [histone H3]-N6,N6-L-dimethyllysine4-1-21 recombinant enzyme, presence of activator CoREST, pH 7.5, 25°C Homo sapiens
0.00889
-
 H3K4me2 1-21 peptide pH 7.5, 25°C, recombinant N-terminally truncated KDM1A-CoREST-Linker complex Homo sapiens
0.00889
-
 [histone H3]-N6,N6-L-dimethyllysine4-1-21 recombinant enzyme, presence of a protein corresponding to the linker region of activator CoREST, pH 7.5, 25°C Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
nucleus
-
 Homo sapiens 5634
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
[histone H3]-N6,N6-dimethyl-L-lysine 4 + 2-oxoglutarate + O2 Homo sapiens
-
 [histone H3]-N6-methyl-L-lysine 4 + succinate + formaldehyde + CO2
-
 ?
[histone H3]-N6-methyl-L-lysine 4 + 2-oxoglutarate + O2 Homo sapiens
-
 [histone H3]-L-lysine 4 + succinate + formaldehyde + CO2
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens O60341
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
H3K4me2 1-21 peptide + 2-oxoglutarate + O2
-
 Homo sapiens H3K4me1 1-21 peptide + succinate + formaldehyde + CO2
-
 ?
additional information the bifunctional enzyme catalyzes the demethylation of H3K4me2/me1 and H3K9me2/me1 (EC 1.14.11.65), as well as non-histone substrates. Tight-binding nature of the H3/KDM1A interaction, kinetics, overview. No other core histones exhibits inhibition of KDM1A demethylation activity, which is consistent with H3 being the preferred histone substrate of KDM1A versus H2A, H2B, and H4. Kinetic analysis of full-length histone products against KDM1A. KDM1A requires a minimal substrate corresponding to the first 21 residues of the N-terminal histone H3 tail for efficient demethylation activity. Recombinant KDM1A/LSD11 forms a complex in vitro with recombinant transcription factor CoREST Homo sapiens ?
-
 ?
[histone H3]-N6,N6-dimethyl-L-lysine 4 + 2-oxoglutarate + O2
-
 Homo sapiens [histone H3]-N6-methyl-L-lysine 4 + succinate + formaldehyde + CO2
-
 ?
[histone H3]-N6,N6-L-dimethyllysine4-1-21 + O2 + 2 H2O substrate is a dimethylated peptide corresponding to the first 21 amino acids of the N-terminal tail of histone H3 Homo sapiens [histone H3]-L-lysine4-1-21 + 2 formaldehyde + 2 H2O2
-
 ?
[histone H3]-N6-methyl-L-lysine 4 + 2-oxoglutarate + O2
-
 Homo sapiens [histone H3]-L-lysine 4 + succinate + formaldehyde + CO2
-
 ?

Subunits

Subunits Comment Organism
More from N- to C-terminus, KDM1A is composed of an unstructured region that contains the nuclear localization signal and three structured domains: a SWI3p, Rsc8p, and Moira (SWIRM) domain, an amine oxidase domain (AOD), and an unprecedented intervening domain within the AOD colloquially known as the tower. The tower domain of KDM1A is composed of two antiparallel alpha-helices (termed TalphaA and TbetaB) that form a coiled coil and extend approximately 100 A from the amine oxidase domain (AOD) Homo sapiens

Synonyms

Synonyms Comment Organism
KDM1A
-
 Homo sapiens
LSD1
-
 Homo sapiens
lysine-specific demethylase 1A
-
 Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
 assay at Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.1
-
 [histone H3]-N6,N6-L-dimethyllysine4-1-21 recombinant enzyme, pH 7.5, 25°C Homo sapiens
0.1
-
 H3K4me2 1-21 peptide pH 7.5, 25°C, recombinant N-terminally truncated KDM1A Homo sapiens
0.157
-
 H3K4me2 1-21 peptide pH 7.5, 25°C, recombinant N-terminally truncated KDM1A-CoREST-Linker complex Homo sapiens
0.157
-
 [histone H3]-N6,N6-L-dimethyllysine4-1-21 recombinant enzyme, presence of a protein corresponding to the linker region of activator CoREST, pH 7.5, 25°C Homo sapiens
0.159
-
 H3K4me2 1-21 peptide pH 7.5, 25°C, recombinant N-terminally truncated KDM1A-CoREST-C complex Homo sapiens
0.159
-
 [histone H3]-N6,N6-L-dimethyllysine4-1-21 recombinant enzyme, presence of activator CoREST, pH 7.5, 25°C Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
 assay at Homo sapiens

Cofactor

Cofactor Comment Organism Structure
FAD dependent on, required for catalysis. THe FAD is noncovalently bound at the amine oxidase domain (AOD) Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.0000189
-
 histone H3 pH 7.5, 25°C Homo sapiens
0.0000189
-
 histone H3 pH 7.5, 25°C, recombinant enzyme Homo sapiens
0.00177
-
 histone H3-1-21 pH 7.5, 25°C Homo sapiens
0.00177
-
 histone H3 1-21 peptide pH 7.5, 25°C, recombinant enzyme Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.000153
-
 pH 7.5, 25°C, recombinant enzyme Homo sapiens histone H3
0.0048
-
 pH 7.5, 25°C Homo sapiens histone H3-1-21
0.00484
-
 pH 7.5, 25°C, recombinant enzyme Homo sapiens histone H3 1-21 peptide

General Information

General Information Comment Organism
additional information although the active site is expanded compared to that of members of the greater amine oxidase superfamily, it is too much sterically restricted to encompass the minimal 21-mer peptide substrate footprint. The remainder of the substrate/product is therefore expected to extend along the surface of KDM1A Homo sapiens
physiological function lysine-specific demethylase 1A (KDM1A/LSD1) is a FAD-dependent enzyme that catalyzes the oxidative demethylation of histone H3K4me1/2 and H3K9me1/2 repressing and activating transcription, respectively Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
17.66
-
 H3K4me2 1-21 peptide pH 7.5, 25°C, recombinant N-terminally truncated KDM1A-CoREST-Linker complex Homo sapiens
17.67
-
 [histone H3]-N6,N6-L-dimethyllysine4-1-21 recombinant enzyme, presence of a protein corresponding to the linker region of activator CoREST, pH 7.5, 25°C Homo sapiens
19.5
-
 [histone H3]-N6,N6-L-dimethyllysine4-1-21 recombinant enzyme, presence of activator CoREST, pH 7.5, 25°C Homo sapiens
19.53
-
 H3K4me2 1-21 peptide pH 7.5, 25°C, recombinant N-terminally truncated KDM1A-CoREST-C complex Homo sapiens
22.42
-
 H3K4me2 1-21 peptide pH 7.5, 25°C, recombinant N-terminally truncated KDM1A Homo sapiens
22.5
-
 [histone H3]-N6,N6-L-dimethyllysine4-1-21 recombinant enzyme, pH 7.5, 25°C Homo sapiens