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Literature summary for 3.5.1.48 extracted from
- Polyamine deacetylase structure and catalysis prokaryotic acetylpolyamine amidohydrolase and eukaryotic HDAC10 (2018), Biochemistry, 57, 3105-3114 .
Application
| Application | Comment | Organism |
|---|---|---|
| drug development | HDAC10 is a biomarker and a target for the design of isozyme-selective inhibitors that will suppress autophagic responses to cancer chemotherapy, thereby rendering cancer cells more susceptible to cytotoxic drugs | Homo sapiens |
| pharmacology | HDAC10 isozyme-selective inhibitors will suppress autophagic responses to cancer chemotherapy, thereby rendering cancer cells more susceptible to cytotoxic drugs | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| 7-[(3-aminopropyl)amino]-1,1,1-trifluoroheptan-2-one | AAT, binds as a tetrahedral gem-diolate to both APAH (acetylpolyamine amidohydrolase, EC 3.5.1.62) and HDAC10, thereby mimicking the tetrahedral intermediate and its flanking transition states in catalysis | Danio rerio |  |
| 7-[(3-aminopropyl)amino]-1,1,1-trifluoroheptan-2-one | AAT, binds as a tetrahedral gem-diolate to both APAH (acetylpolyamine amidohydrolase, EC 3.5.1.62) and HDAC10, thereby mimicking the tetrahedral intermediate and its flanking transition states in catalysis | Homo sapiens | |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Zn2+ | catalytic zinc ion | Homo sapiens | |
| Zn2+ | catalytic zinc ion | Danio rerio | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| N8-acetylspermidine + H2O | Homo sapiens | - |
acetate + spermidine | - |
? | |
| N8-acetylspermidine + H2O | Danio rerio | - |
acetate + spermidine | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Danio rerio | F1QCV2 | - |
- |
| Homo sapiens | Q969S8 | - |
- |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | histone deacetylase 10 (HDAC10) from Danio rerio is a highly specific N8-acetylspermidine deacetylase. No activity with N1-acetylspermidine and N1-acetylspermine | Danio rerio | ? | - |
? | |
| additional information | histone deacetylase 10 (HDAC10) from Homo sapiens is a highly specific N8-acetylspermidine deacetylase. No activity with N1-acetylspermidine and N1-acetylspermine | Homo sapiens | ? | - |
? | |
| N8-acetylspermidine + H2O | - |
Homo sapiens | acetate + spermidine | - |
? | |
| N8-acetylspermidine + H2O | - |
Danio rerio | acetate + spermidine | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| HDAC10 | - |
Homo sapiens |
| HDAC10 | - |
Danio rerio |
| histone deacetylase 10 | - |
Homo sapiens |
| histone deacetylase 10 | - |
Danio rerio |
| polyamine deacetylase | - |
Homo sapiens |
| polyamine deacetylase | - |
Danio rerio |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | the enzyme adopts the characteristic arginase-deacetylase fold and employ a Zn2+-activated water molecule for catalysis. The active sites of HDAC10 and APAH (acetylpolyamine amidohydrolase, EC 3.5.1.62) are sterically constricted to enforce specificity for long, slender polyamine substrates and exclude bulky peptides and proteins containing acetyl-L-lysine. The tertiary structure (a unique 310 helix defined by the P(E,A)CE motif) provides the steric constriction that directs the polyamine substrate specificity of HDAC10. Structure and catalytic mechanism of polyamine deacetylases, comparison of HDAC and APAH, overview | Homo sapiens |
| evolution | the enzyme adopts the characteristic arginase-deacetylase fold and employ a Zn2+-activated water molecule for catalysis. The active sites of HDAC10 and APAH (acetylpolyamine amidohydrolase, EC 3.5.1.62) are sterically constricted to enforce specificity for long, slender polyamine substrates and exclude bulky peptides and proteins containing acetyl-L-lysine. The tertiary structure (a unique 310 helix defined by the P(E,A)CE motif) provides the steric constriction that directs the polyamine substrate specificity of HDAC10. Structure and catalytic mechanism of polyamine deacetylases, comparison of HDAC and APAH, overview | Danio rerio |
| additional information | nucleophilic attack of Zn2+-bound water at the amide carbonyl group polarized by Zn2+ and the catalytic tyrosine is facilitated by a general base. The Zn2+ ion, tyrosine, and tandem histidine residues contribute to transition state stabilization in each deacetylase. Collapse of the tetrahedral intermediate requires a proton donor, and the second histidine of the tandem pair must serve as the general acid due to its proximity to the leaving amino group. Structure-function analysis of substrate specificity, overview | Homo sapiens |
| additional information | nucleophilic attack of Zn2+-bound water at the amide carbonyl group polarized by Zn2+ and the catalytic tyrosine is facilitated by a general base. The Zn2+ ion, tyrosine, and tandem histidine residues contribute to transition state stabilization in each deacetylase. Collapse of the tetrahedral intermediate requires a proton donor, and the second histidine of the tandem pair must serve as the general acid due to its proximity to the leaving amino group. Structure-function analysis of substrate specificity, overview | Danio rerio |
| physiological function | HDAC10 and spermidine act as mediators of autophagy | Homo sapiens |
| physiological function | HDAC10 and spermidine act as mediators of autophagy | Danio rerio |
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