Application | Comment | Organism |
---|---|---|
drug development | Drug repurposing of histone deacetylase inhibitors that alleviate neutrophilic inflammation in acute lung injury and idiopathic pulmonary fibrosis via inhibiting leukotriene A4 hydrolase and blocking LTB4 biosynthesis | Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
enzyme in complex with inhibitors SAHA or M344, X-ray diffraction structure determination and analysis | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(S)-2-((2S,3R)-3-amino-2-hydroxy-4-phenylbutanamido)-4-methylpentanoic acid | - |
Homo sapiens | |
3-[methyl[3-[4-(phenylmethyl)phenoxy]propyl]amino]-propanoic acid | - |
Homo sapiens | |
4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]benzamide | enzyme binding structure, overview | Homo sapiens | |
abexinostat | - |
Homo sapiens | |
belinostat | - |
Homo sapiens | |
CUDC-101 | - |
Homo sapiens | |
entinostat | - |
Homo sapiens | |
givinostat | - |
Homo sapiens | |
JNJ-26481585 | - |
Homo sapiens | |
mocetinostat | - |
Homo sapiens | |
additional information | drug repurposing of histone deacetylase (HDAC) inhibitors that alleviate neutrophilic inflammation in acute lung injury and idiopathic pulmonary fibrosis via inhibiting leukotriene A4 hydrolase and blocking LTB4 biosynthesis, overview. Analysis of potential inhibitors of LTA4H across a panel of 18 HDAC inhibitors, using enzymatic assay, thermofluor assay, and X-ray crystallographic investigation. Detailed mechanisms of down-regulation of proinflammatory cytokines by SAHA or M344 are determined in vivo. Cotreatment of N-(6-(2-aminophenylamino)-6-oxyhexyl)-4-methylbenzamide and (S)-2-((2S,3R)-3-amino-2-hydroxy-4-phenylbutanamido)-4-methylpentanoic acid synergistically represses the migration of neutrophil and LTB4-induced neutrophil migration is not affected by these treatments. Molecular modeling of HDAC inhibitors against LTA4H hydrolase and aminopeptidase | Homo sapiens | |
N-(6-(2-aminophenylamino)-6-oxyhexyl)-4-methylbenzamide | - |
Homo sapiens | |
panobinostat | - |
Homo sapiens | |
pracinostat | - |
Homo sapiens | |
resminostat | - |
Homo sapiens | |
rocilinostat | - |
Homo sapiens | |
scriptaid | - |
Homo sapiens | |
suberanilohydroxamic acid | enzyme binding structure, overview | Homo sapiens | |
trichostatin A | - |
Homo sapiens | |
tubacin | - |
Homo sapiens | |
Valproate | - |
Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Zn2+ | zinc metalloenzyme, enzyme LTA4H folds into three domains and creates a deep cleft harboring the catalytic Zn2+ site, forming the active site with an L-shaped hydrophobic pocket deep into the protein | Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P09960 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
neutrophil | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | the aminopeptidase binding site shares a similar structure to LTA4H (EC 3.3.2.6) at its ligand binding sites | Homo sapiens | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
More | LTA4H folds into three domains and creates a deep cleft harboring the catalytic Zn2+ site, forming the active site with an L-shaped hydrophobic pocket deep into the protein | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
Aminopeptidase | - |
Homo sapiens |
More | see also EC 3.3.2.6 | Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0003 | - |
pH and temperature not specified in the publication | Homo sapiens | 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]benzamide | |
0.00167 | - |
pH and temperature not specified in the publication | Homo sapiens | suberanilohydroxamic acid | |
0.0044 | - |
pH and temperature not specified in the publication | Homo sapiens | scriptaid | |
0.01 | - |
above, pH and temperature not specified in the publication | Homo sapiens | trichostatin A | |
0.01 | - |
above, pH and temperature not specified in the publication | Homo sapiens | Valproate | |
0.01 | - |
above, pH and temperature not specified in the publication | Homo sapiens | tubacin | |
0.01 | - |
above, pH and temperature not specified in the publication | Homo sapiens | JNJ-26481585 | |
0.01 | - |
above, pH and temperature not specified in the publication | Homo sapiens | belinostat | |
0.01 | - |
above, pH and temperature not specified in the publication | Homo sapiens | entinostat | |
0.01 | - |
above, pH and temperature not specified in the publication | Homo sapiens | panobinostat | |
0.01 | - |
above, pH and temperature not specified in the publication | Homo sapiens | mocetinostat | |
0.01 | - |
above, pH and temperature not specified in the publication | Homo sapiens | resminostat | |
0.01 | - |
above, pH and temperature not specified in the publication | Homo sapiens | abexinostat | |
0.01 | - |
above, pH and temperature not specified in the publication | Homo sapiens | CUDC-101 | |
0.01 | - |
above, pH and temperature not specified in the publication | Homo sapiens | givinostat | |
0.01 | - |
above, pH and temperature not specified in the publication | Homo sapiens | N-(6-(2-aminophenylamino)-6-oxyhexyl)-4-methylbenzamide | |
0.01 | - |
above, pH and temperature not specified in the publication | Homo sapiens | pracinostat | |
0.01 | - |
above, pH and temperature not specified in the publication | Homo sapiens | rocilinostat |
General Information | Comment | Organism |
---|---|---|
malfunction | LTB4 levels are persistently elevated in bronchoalveolar lavage fluid (BALF) of lipopolysaccharide (LPS)-induced ALI, and the leukotriene levels in pulmonary edema fluid are significantly higher in ALI patients compared to control patients with hydrostatic pulmonary edema. In addition, LTB4 level is increased in lung homogenates, and BALF of patients with IPF and the level of LTB4 correlate with the extent of fibrosis in histological sections | Homo sapiens |
additional information | LTA4H folds into three domains and creates a deep cleft harboring the catalytic Zn2+ site, forming the active site with an L-shaped hydrophobic pocket deep into the protein | Homo sapiens |
physiological function | leukotriene A4 hydrolase (LTA4H) is a bifunctional enzyme that exhibits LTA4H and aminopeptidase activities, it is a key enzyme in the biosynthesis of leukotriene B4 (LTB4). LTA4H is well-known to regulate chemotactic activity of human neutrophils. LTB4 is secreted by neutrophils at inflammation sites in response to formyl peptides, playing an important role in neutrophil activation and migration to formyl peptides | Homo sapiens |