3CHQ

Crystal structure of leukotriene a4 hydrolase in complex with N5-[4-(phenylmethoxy)phenyl]-L-glutamine

3CHQ の概要

• エントリーDOI: 10.2210/pdb3chq/pdb
• 関連するPDBエントリー: 1GW6 1H19 1HS6 1SQM 2VJ8 3CHO 3CHP 3CHR 3CHS
• 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: epoxide hydrolase, alpha-beta protein, leukotriene biosynthesis, metalloprotease, inhibitor complex, alternative splicing, cytoplasm, metal-binding, multifunctional enzyme, zinc, 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: 70214.75

構造登録者

Thunnissen, M.M.G.M.,Adler, M.,Whitlow, M. (登録日: 2008-03-10, 公開日: 2008-04-22, 最終更新日: 2024-02-21)

主引用文献

Kirkland, T.A.,Adler, M.,Bauman, J.G.,Chen, M.,Haeggstrom, J.Z.,King, B.,Kochanny, M.J.,Liang, A.M.,Mendoza, L.,Phillips, G.B.,Thunnissen, M.,Trinh, L.,Whitlow, M.,Ye, B.,Ye, H.,Parkinson, J.,Guilford, W.J.
Synthesis of glutamic acid analogs as potent inhibitors of leukotriene A4 hydrolase.
Bioorg.Med.Chem., 16:4963-4983, 2008

PubMed Abstract: Leukotriene B(4) (LTB(4)) is a potent pro-inflammatory mediator that has been implicated in the pathogenesis of multiple diseases, including psoriasis, inflammatory bowel disease, multiple sclerosis and asthma. As a method to decrease the level of LTB(4) and possibly identify novel treatments, inhibitors of the LTB(4) biosynthetic enzyme, leukotriene A(4) hydrolase (LTA(4)-h), have been explored. Here we describe the discovery of a potent inhibitor of LTA(4)-h, arylamide of glutamic acid 4f, starting from the corresponding glycinamide 2. Analogs of 4f are then described, focusing on compounds that are both active and stable in whole blood. This effort culminated in the identification of amino alcohol 12a and amino ester 6b which meet these criteria.

PubMed: 18394906
DOI: 10.1016/j.bmc.2008.03.042

実験手法

X-RAY DIFFRACTION (2.09 Å)