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Literature summary for 3.3.2.6 extracted from
- Thermodynamic properties of leukotriene A4 hydrolase inhibitors (2016), Bioorg. Med. Chem., 24, 5243-5248 .
Application
| Application | Comment | Organism |
|---|---|---|
| drug development | the bifunctional enzyme is a target for development of selective inhibitors | Homo sapiens |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| recombinant expression of human LTA4H with C-terminal hexahistidine tag and N-terminal T7 gene leader sequence | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| ARM1 | - |
Homo sapiens |  |
| bestatin | - |
Homo sapiens | |
| captopril | - |
Homo sapiens | |
| additional information | thermodynamic properties of structurally distinct leukotriene A4 hydrolase inhibitors. An in silico method for the determination of stabilized water molecules in the binding site of the apo structure of LTA4H is used to interpret the measured thermodynamic data and provided insights for design of novel LTA4H inhibitors. Fluorescence-based assay system with recombinant His6-tagged enzyme is used for determination of the inhibition kinetics | Homo sapiens | |
| RB202 | - |
Homo sapiens | |
| SC57461A | - |
Homo sapiens | |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Zn2+ | the zinc ion is essential for both catalytic activities of LTA4H, it is coordinated by three amino acid residues (His295, His299, Glu318) located in the catalytic domain | Homo sapiens | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| leukotriene A4 + H2O | Homo sapiens | - |
leukotriene B4 | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | P09960 | - |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant His6-tagged enzyme by nickel affinity chromatography and gel filtration | Homo sapiens |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| L-arginine-7-amido-4-methylcoumarine + H2O | an artificial substrate | Homo sapiens | L-arginine + 4-methylcoumarin-7-amine | - |
? | |
| leukotriene A4 + H2O | - |
Homo sapiens | leukotriene B4 | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| dimer | 2 * 69000, SDS-PAGE | Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| leukotriene A4 hydrolase | - |
Homo sapiens |
| LTA4H | - |
Homo sapiens |
Ki Value [mM]
| Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.000003 | - |
SC57461A | pH and temperature not specified in the publication | Homo sapiens | |
| 0.00016 | - |
RB202 | pH and temperature not specified in the publication | Homo sapiens | |
| 0.00032 | - |
bestatin | pH and temperature not specified in the publication | Homo sapiens | |
| 0.00036 | - |
ARM1 | pH and temperature not specified in the publication | Homo sapiens | |
| 0.0037 | - |
captopril | pH and temperature not specified in the publication | Homo sapiens | |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.000006 | - |
pH and temperature not specified in the publication | Homo sapiens | SC57461A | |
| 0.00006 | - |
pH and temperature not specified in the publication | Homo sapiens | RB202 | |
| 0.0003 | - |
pH and temperature not specified in the publication | Homo sapiens | bestatin | |
| 0.0004 | - |
pH and temperature not specified in the publication | Homo sapiens | ARM1 | |
| 0.0036 | - |
pH and temperature not specified in the publication | Homo sapiens | captopril | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | inhibition of the LTB4 conversion ameliorates inflammation and leads to accumulation of pro-resolving Lipoxin A4 (LXA4) while inhibition of PGP degradation potentiates neutrophilic inflammation | Homo sapiens |
| additional information | binding pocket of the apo LTA4H protein (PDB entry 5FWQ) with bound Zn2+, overview | Homo sapiens |
| physiological function | the human leukotriene A4 hydrolase (LTA4H) is a 69 kDa protein involved in the arachidonic acid cascade. LTA4H converts leukotriene A4 (LTA4) into leukotriene B4 (LTB4).1 LTB4 triggers the adhesion and aggregation of leukocytes in the endothelium2 and acts as an attractant for different leukocytes (monocytes, neutrophils, macrophages, and dendritic cells). The overproduction of LTB4 has been associated with different pathological conditions and diseases. The leukotriene A4 hydrolase (LTA4H) is a bifunctional enzyme, containing a peptidase and a hydrolase activity both activities having opposing functions regulating inflammatory response. The hydrolase activity is responsible for the conversion of leukotriene A4 to pro-inflammatory leukotriene B4 | Homo sapiens |
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