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Literature summary for 1.14.99.66 extracted from
- LSD1: oxidative chemistry for multifaceted functions in chromatin regulation (2008), Trends Biochem. Sci., 33, 181-189.
Application
| Application | Comment | Organism |
|---|---|---|
| drug development | potential pharmacological value of LSD1 as a drug target originating from it being a flavin-dependent demethylase, rather than an iron-dependent enzyme of the Jumonji class | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| biguanide | inhibits LSD1 and is capable of reactivating genes that are pathologically silenced in the development of colon cancer | Homo sapiens |  |
| bisguanidine polyamine analogues | inhibit LSD1 and are capable of reactivating genes that are pathologically silenced in the development of colon cancer | Homo sapiens | |
| additional information | design and development of LSD1 inhibitors, overview | Homo sapiens | |
| tranylcypromine | inhibits LSD1 by forming a covalent adduct with the flavin moiety through the opening of the inhibitor cyclopropyl ring, binding structure, overview | Drosophila melanogaster | |
| tranylcypromine | inhibits LSD1 by forming a covalent adduct with the flavin moiety through the opening of the inhibitor cyclopropyl ring, binding structure, overview | Homo sapiens | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | Drosophila melanogaster | LSD1 interacts with several interaction partners and transcription factors for performing its role in gene regulation, overview | ? | - |
? | |
| additional information | Homo sapiens | LSD1 interacts with several interaction partners and transcription factors for performing its role in gene regulation, overview. LSD1 forms a complex with CoREST, structure with bound histone H3 peptide substrate, overview. LSD1 tightly associates with the CoREST C-terminal SANT domain. This intermolecular association is mediated by the LSD1 tower domain, whose alpha-helices are embraced by a helical segment of CoREST, generating an intermolecular helical coil. The histone H3 N-terminal peptide binds deeply in the LSD1 amine oxidase domain in proximity to the flavin cofactor | ? | - |
? | |
| [histone H3]-N6,N6-dimethyl-L-lysine4 + 2 2-oxoglutarate + 2 O2 | Drosophila melanogaster | dimethyl-H3K4 is an activation markers for gene expression | [histone H3]-L-lysine4 + 2 succinate + 2 formaldehyde + 2 CO2 | - |
? | |
| [histone H3]-N6,N6-dimethyl-L-lysine4 + 2 2-oxoglutarate + 2 O2 | Homo sapiens | dimethyl-H3K4 is an activation markers for gene expression | [histone H3]-L-lysine4 + 2 succinate + 2 formaldehyde + 2 CO2 | - |
? | |
| [histone H3]-N6,N6-methyl-L-lysine4 + 2-oxoglutarate + O2 | Drosophila melanogaster | - |
[histone H3]-L-lysine4 + succinate + formaldehyde + CO2 | - |
? | |
| [histone H3]-N6,N6-methyl-L-lysine4 + 2-oxoglutarate + O2 | Homo sapiens | - |
[histone H3]-L-lysine4 + succinate + formaldehyde + CO2 | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Drosophila melanogaster | - |
- |
- |
| Homo sapiens | O75164 | - |
- |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | LSD1 interacts with several interaction partners and transcription factors for performing its role in gene regulation, overview | Drosophila melanogaster | ? | - |
? | |
| additional information | LSD1 interacts with several interaction partners and transcription factors for performing its role in gene regulation, overview. LSD1 forms a complex with CoREST, structure with bound histone H3 peptide substrate, overview. LSD1 tightly associates with the CoREST C-terminal SANT domain. This intermolecular association is mediated by the LSD1 tower domain, whose alpha-helices are embraced by a helical segment of CoREST, generating an intermolecular helical coil. The histone H3 N-terminal peptide binds deeply in the LSD1 amine oxidase domain in proximity to the flavin cofactor | Homo sapiens | ? | - |
? | |
| additional information | LSD1 catalyzes the demethylation of Lys4 of histone H3 through a flavin-dependent oxidative reaction via an imine intermediate. LSD1 can act both on mono- and dimethylated H3K4. The reaction involves several steps, overview | Drosophila melanogaster | ? | - |
? | |
| additional information | LSD1 catalyzes the demethylation of Lys4 of histone H3 through a flavin-dependent oxidative reaction via an imine intermediate. LSD1 can act both on mono- and dimethylated H3K4. The reaction involves several steps, overview | Homo sapiens | ? | - |
? | |
| [histone H3]-N6,N6-dimethyl-L-lysine4 + 2 2-oxoglutarate + 2 O2 | - |
Drosophila melanogaster | [histone H3]-L-lysine4 + 2 succinate + 2 formaldehyde + 2 CO2 | - |
? | |
| [histone H3]-N6,N6-dimethyl-L-lysine4 + 2 2-oxoglutarate + 2 O2 | dimethyl-H3K4 is an activation markers for gene expression | Drosophila melanogaster | [histone H3]-L-lysine4 + 2 succinate + 2 formaldehyde + 2 CO2 | - |
? | |
| [histone H3]-N6,N6-dimethyl-L-lysine4 + 2 2-oxoglutarate + 2 O2 | dimethyl-H3K4 is an activation markers for gene expression | Homo sapiens | [histone H3]-L-lysine4 + 2 succinate + 2 formaldehyde + 2 CO2 | - |
? | |
| [histone H3]-N6,N6-dimethyl-L-lysine4 + 2 2-oxoglutarate + 2 O2 | specific pockets in the substrate-binding site of LSD1 that interact with several H3 side chains, Thr6, Arg8, Lys9 and Thr11, and also with the N-terminal amino group of Ala1, N-term pocket, overview | Homo sapiens | [histone H3]-L-lysine4 + 2 succinate + 2 formaldehyde + 2 CO2 | - |
? | |
| [histone H3]-N6,N6-methyl-L-lysine4 + 2-oxoglutarate + O2 | - |
Drosophila melanogaster | [histone H3]-L-lysine4 + succinate + formaldehyde + CO2 | - |
? | |
| [histone H3]-N6,N6-methyl-L-lysine4 + 2-oxoglutarate + O2 | - |
Homo sapiens | [histone H3]-L-lysine4 + succinate + formaldehyde + CO2 | - |
? | |
| [histone H3]-N6,N6-methyl-L-lysine4 + 2-oxoglutarate + O2 | specific pockets in the substrate-binding site of LSD1 that interact with several H3 side chains, Thr6, Arg8, Lys9 and Thr11, and also with the N-terminal amino group of Ala1, N-term pocket | Homo sapiens | [histone H3]-L-lysine4 + succinate + formaldehyde + CO2 | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| H3K4 demethylase | - |
Drosophila melanogaster |
| H3K4 demethylase | - |
Homo sapiens |
| LSD1 | - |
Drosophila melanogaster |
| LSD1 | - |
Homo sapiens |
| lysine-specific demethylase 1 | - |
Drosophila melanogaster |
| lysine-specific demethylase 1 | - |
Homo sapiens |
| More | the enzyme belongs to the flavin-dependent amine oxidases | Drosophila melanogaster |
| More | the enzyme belongs to the flavin-dependent amine oxidases | Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| flavin | dependent on | Drosophila melanogaster | |
| flavin | dependent on | Homo sapiens | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| physiological function | extensive involvement of LSD1 in gene activation, rather than repression | Drosophila melanogaster |
| physiological function | generally LSD1 shows an extensive involvement in gene activation, rather than repression, dual role of LSD1 in gene repression and activation is demonstrated by the fine regulation of growth hormone expression during pituitary development | Homo sapiens |
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