Leukotriene A4 Hydrolase

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Function

Leukotriene A4 Hydrolase (LTA4H) is an aminopeptidase which converts leukotriene A4 to leukotriene B4 as part of the arachidonic acid metabolism[1] . LTA4H is a bifunctional Zn+2 enzyme.

Relevance

LTA4H inhibitors have potential in targeting chronic, autoimmune-driven inflammation[2] .

Disease

Mutations in LTA4H are linked to susceptibility to asthma and to cardiovascular disease.

Structural highlights

LTA4H structure shows . The catalytic domain is made of 2 lobes: an α-helical one and an α/β one. The is located between the 2 lobes and [3]. Water molecules shown as red spheres.

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Human leukotriene A4 Hydrolase complex with bestatin, acetate, imidazole, Yb+3 (green) and Zn+2 (grey) ions (PDB entry 1hs6)

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3D Structures of Leukotriene A4 Hydrolase3D Structures of Leukotriene A4 Hydrolase

Updated on 18-June-2023

ReferencesReferences

  1. ↑ 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
  2. ↑ Fourie AM. Modulation of inflammatory disease by inhibitors of leukotriene A4 hydrolase. Curr Opin Investig Drugs. 2009 Nov;10(11):1173-82. PMID:19876785
  3. ↑ 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

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