Leukotriene A4 Hydrolase
From Proteopedia
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| - | <StructureSection load=' | + | <StructureSection load='' size='350' side='right' caption='Human leukotriene A4 Hydrolase complex with bestatin, acetate, imidazole, Yb+3 (green) and Zn+2 (grey) ions (PDB entry [[1hs6]])' scene='43/433034/Cv/1'> |
== Function == | == Function == | ||
| - | [[Leukotriene A4 Hydrolase]] (LTA4H) is an aminopeptidase which converts leukotriene A4 to leukotriene B4 as part of the arachidonic acid metabolism<ref>PMID:24771855</ref> . | + | [[Leukotriene A4 Hydrolase]] (LTA4H) is an aminopeptidase which converts leukotriene A4 to leukotriene B4 as part of the arachidonic acid metabolism<ref>PMID:24771855</ref> . LTA4H is a bifunctional Zn+2 enzyme. |
== Relevance == | == Relevance == | ||
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Mutations in LTA4H are linked to susceptibility to asthma and to cardiovascular disease. | Mutations in LTA4H are linked to susceptibility to asthma and to cardiovascular disease. | ||
| + | == Structural highlights == | ||
| + | LTA4H structure shows <scene name='43/433034/Cv/10'>3 domains: N-terminal, catalytic and C-terminal</scene>. The catalytic domain is made of 2 lobes: an α-helical one and an α/β one. The <scene name='43/433034/Cv/11'>catalytic site</scene> is located between the 2 lobes and <scene name='43/433034/Cv/12'>contains a Zn+2 ion</scene><ref>PMID:11175901</ref>. Water molecules shown as red spheres. | ||
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| + | <scene name='43/433034/Cv/8'>1st Yb coordination site</scene>. | ||
| + | |||
| + | <scene name='43/433034/Cv/9'>2nd Yb coordination site</scene>. | ||
| + | </StructureSection> | ||
== 3D Structures of Leukotriene A4 Hydrolase == | == 3D Structures of Leukotriene A4 Hydrolase == | ||
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* LTA4H | * LTA4H | ||
| - | **[[ | + | **[[4rvb]], [[5fwq]] - hLTA4H – human<br /> |
| - | **[[1sqm]], [[1gw6]], [[1h19]] - hLTA4H (mutant) | + | **[[1sqm]], [[1gw6]], [[1h19]] - hLTA4H (mutant) <br /> |
| + | **[[1xpy]], [[2xpy]], [[2xpz]] – yLTA4H – yeast<br /> | ||
* LTA4H + inhibitor | * LTA4H + inhibitor | ||
| - | **[[2xq0]] – yLTA4H+bestatin<br /> | ||
**[[3fh5]], [[3fh7]], [[3fh8]], [[3fhe]], [[3ful]], [[3fum]], [[3fun]] - hLTA4H+pyrrolidine inhibitor | **[[3fh5]], [[3fh7]], [[3fh8]], [[3fhe]], [[3ful]], [[3fum]], [[3fun]] - hLTA4H+pyrrolidine inhibitor | ||
**[[1hs6]] - hLTA4H+bestatin<br /> | **[[1hs6]] - hLTA4H+bestatin<br /> | ||
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**[[3fue]], [[3fuf]], [[3fuh]] - hLTA4H+bestatin+indole derivative<br /> | **[[3fue]], [[3fuf]], [[3fuh]] - hLTA4H+bestatin+indole derivative<br /> | ||
**[[3fuj]], [[3fuk]] - hLTA4H+indole derivative<br /> | **[[3fuj]], [[3fuk]] - hLTA4H+indole derivative<br /> | ||
| - | **[[3b7r]], [[3cho]], [[3chp]], [[3chq]], [[3chr]], [[3chs]], [[2r59]], [[3u9w]], [[5aen]] - hLTA4H+inhibitor<br /> | + | **[[3b7r]], [[3cho]], [[3chp]], [[3chq]], [[3chr]], [[3chs]], [[2r59]], [[3u9w]], [[4r7l]], [[4rsy]], [[5aen]], [[5bpp]], [[6enc]], [[6end]], [[7auz]], [[7av0]], [[7av1]], [[7av2]], [[8ava]], [[8awh]] - hLTA4H+inhibitor<br /> |
**[[3b7u]] - hLTA4H+kelatorphan <br /> | **[[3b7u]] - hLTA4H+kelatorphan <br /> | ||
**[[2vj8]] - hLTA4H+hydroxamic acid<br /> | **[[2vj8]] - hLTA4H+hydroxamic acid<br /> | ||
**[[4dpr]] – hLTA4H + captopril<br /> | **[[4dpr]] – hLTA4H + captopril<br /> | ||
| - | **[[3b7s]], [[3b7t]] - hLTA4H (mutant)+tripeptide<br /> | + | **[[4ms6]], [[7kze]], [[7llq]] - hLTA4H +tripeptide analog <br /> |
| + | **[[4l2l]] - hLTA4H + thiazol derivative<br /> | ||
| + | **[[4mkt]] - hLTA4H +tripeptide analog + thiazol derivative<br /> | ||
| + | **[[3b7s]], [[3b7t]], [[6enb]] - hLTA4H (mutant)+tripeptide<br /> | ||
| + | **[[6o5h]] – hLTA4H + modifier<br /> | ||
| + | **[[4gaa]] - LTA4H+bestatin – frog<br /> | ||
| + | **[[2xq0]] – yLTA4H+bestatin<br /> | ||
}} | }} | ||
| - | + | == References == | |
<references/> | <references/> | ||
[[Category:Topic Page]] | [[Category:Topic Page]] | ||
Current revision
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3D Structures of Leukotriene A4 Hydrolase
Updated on 18-June-2023
References
- ↑ Paige M, Wang K, Burdick M, Park S, Cha J, Jeffery E, Sherman N, Shim YM. Role of leukotriene A4 hydrolase aminopeptidase in the pathogenesis of emphysema. J Immunol. 2014 Jun 1;192(11):5059-68. doi: 10.4049/jimmunol.1400452. Epub 2014, Apr 25. PMID:24771855 doi:http://dx.doi.org/10.4049/jimmunol.1400452
- ↑ Fourie AM. Modulation of inflammatory disease by inhibitors of leukotriene A4 hydrolase. Curr Opin Investig Drugs. 2009 Nov;10(11):1173-82. PMID:19876785
- ↑ Thunnissen MM, Nordlund P, Haeggstrom JZ. Crystal structure of human leukotriene A(4) hydrolase, a bifunctional enzyme in inflammation. Nat Struct Biol. 2001 Feb;8(2):131-5. PMID:11175901 doi:10.1038/84117
