1HS6

STRUCTURE OF LEUKOTRIENE A4 HYDROLASE COMPLEXED WITH BESTATIN.

1HS6 の概要

• エントリーDOI: 10.2210/pdb1hs6/pdb
• 分子名称: LEUKOTRIENE A-4 HYDROLASE, ZINC ION, YTTERBIUM (III) ION, ... (7 entities in total)
• 機能のキーワード: protein-inhibitor complex, alpha-beta protein, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 70385.00

構造登録者

Thunnissen, M.M.G.M.,Nordlund, P.N.,Haeggstrom, J.Z. (登録日: 2000-12-24, 公開日: 2001-06-24, 最終更新日: 2024-03-13)

主引用文献

Thunnissen, M.M.,Nordlund, P.,Haeggstrom, J.Z.
Crystal structure of human leukotriene A(4) hydrolase, a bifunctional enzyme in inflammation.
Nat.Struct.Biol., 8:131-135, 2001

PubMed Abstract: Leukotriene (LT) A(4) hydrolase/aminopeptidase (LTA4H) is a bifunctional zinc enzyme that catalyzes the biosynthesis of LTB4, a potent lipid chemoattractant involved in inflammation, immune responses, host defense against infection, and PAF-induced shock. The high resolution crystal structure of LTA4H in complex with the competitive inhibitor bestatin reveals a protein folded into three domains that together create a deep cleft harboring the catalytic Zn(2+) site. A bent and narrow pocket, shaped to accommodate the substrate LTA(4), constitutes a highly confined binding region that can be targeted in the design of specific anti-inflammatory agents. Moreover, the structure of the catalytic domain is very similar to that of thermolysin and provides detailed insight into mechanisms of catalysis, in particular the chemical strategy for the unique epoxide hydrolase reaction that generates LTB(4).

PubMed: 11175901
DOI: 10.1038/84117

実験手法

X-RAY DIFFRACTION (1.95 Å)