2R59

Leukotriene A4 hydrolase complexed with inhibitor RB3041

2R59 の概要

• エントリーDOI: 10.2210/pdb2r59/pdb
• 関連するPDBエントリー: 1GW6 1H19 1HS6 1SQM
• 分子名称: Leukotriene A-4 hydrolase, ZINC ION, YTTERBIUM (III) ION, ... (6 entities in total)
• 機能のキーワード: transition state, analogue peptide, hydrolysis, alternative splicing, cytoplasm, hydrolase, leukotriene biosynthesis, metal-binding, metalloprotease, multifunctional enzyme, protease, zinc
• 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: 70854.67

構造登録者

Tholander, F.,Haeggstrom, J.Z.,Thunnissen, M.,Muroya, A.,Roques, B.P.,Fournie-Zaluski, M.C. (登録日: 2007-09-03, 公開日: 2008-08-12, 最終更新日: 2024-04-03)

主引用文献

Tholander, F.,Muroya, A.,Roques, B.P.,Fournie-Zaluski, M.C.,Thunnissen, M.M.,Haeggstrom, J.Z.
Structure-based dissection of the active site chemistry of leukotriene a4 hydrolase: implications for m1 aminopeptidases and inhibitor design.
Chem.Biol., 15:920-929, 2008

PubMed Abstract: M1 aminopeptidases comprise a large family of biologically important zinc enzymes. We show that peptide turnover by the M1 prototype, leukotriene A4 hydrolase/aminopeptidase, involves a shift in substrate position associated with exchange of zinc coordinating groups, while maintaining the overall coordination geometry. The transition state is stabilized by residues conserved among M1 members and in the final reaction step, Glu-296 of the canonical zinc binding HEXXH motif shuffles a proton from the hydrolytic water to the leaving group. Tripeptide substrates bind along the conserved GXMEN motif, precisely occupying the distance between Glu-271 and Arg-563, whereas the Arg specificity is governed by a narrow S1 pocket capped with Asp-375. Our data provide detailed insights to the active site chemistry of M1 aminopeptidases and will aid in the development of novel enzyme inhibitors.

PubMed: 18804029
DOI: 10.1016/j.chembiol.2008.07.018

実験手法

X-RAY DIFFRACTION (1.89 Å)