2BM2

human beta-II tryptase in complex with 4-(3-Aminomethyl-phenyl)- piperidin-1-yl-(5-phenethyl- pyridin-3-yl)-methanone

2BM2 の概要

• エントリーDOI: 10.2210/pdb2bm2/pdb
• 関連するPDBエントリー: 1A0L 1AAO
• 分子名称: HUMAN BETA2 TRYPTASE, 1-[3-(1-{[5-(2-PHENYLETHYL)PYRIDIN-3-YL]CARBONYL}PIPERIDIN-4-YL)PHENYL]METHANAMINE (3 entities in total)
• 機能のキーワード: serine protease inhibitor, glycoprotein, hydrolase, polymorphism, protease, serine protease
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 111563.82

構造登録者

Maignan, S.,Guilloteau, J.-P.,Dupuy, A.,Levell, J.,Astles, P.,Eastwood, P.,Cairns, J.,Houille, O.,Aldous, S.,Merriman, G.,Whiteley, B.,Pribish, J.,Czekaj, M.,Liang, G.,Davidson, J.,Harrison, T.,Morley, A.,Watson, S.,Fenton, G.,Mccarthy, C.,Romano, J.,Mathew, R.,Engers, D.,Gardyan, M.,Sides, K.,Kwong, J.,Tsay, J.,Rebello, S.,Shen, L.,Wang, J.,Luo, Y.,Giardino, O.,Lim, H.-K.,Smith, K.,Pauls, H. (登録日: 2005-03-09, 公開日: 2005-03-22, 最終更新日: 2024-11-13)

主引用文献

Levell, J.,Astles, P.,Eastwood, P.,Cairns, J.,Houille, O.,Aldous, S.,Merriman, G.,Whitley, B.,Pribish, J.,Czekaj, M.,Liang, G.,Maignan, S.,Guilloteau, J.-P.,Dupuy, A.,Davidson, J.,Harrison, T.,Morley, A.,Watson, S.,Fenton, G.,Mccarthy, C.,Romano, J.,Mathew, R.,Engers, D.,Gardyan, M.,Sides, K.,Kwong, J.,Tsay, J.,Rebello, S.,Shen, L.,Wang, J.,Luo, Y.,Giardino, O.,Lim, H.-K.,Smith, K.,Pauls, H.
Structure Based Design of 4-(3-Aminomethylphenyl) Piperidinyl-1-Amides: Novel, Potent, Selective, and Orally Bioavailable Inhibitors of Bii Tryptase
Bioorg.Med.Chem., 13:2859-, 2005

PubMed Abstract: Tryptase is a serine protease found almost exclusively in mast cells. It has trypsin-like specificity, favoring cleavage of substrates with an arginine (or lysine) at the P1 position, and has optimal catalytic activity at neutral pH. Current evidence suggests tryptase beta is the most important form released during mast cell activation in allergic diseases. It is shown to have numerous pro-inflammatory cellular activities in vitro, and in animal models tryptase provokes broncho-constriction and induces a cellular inflammatory infiltrate characteristic of human asthma. Screening of in-house inhibitors of factor Xa (a closely related serine protease) identified beta-amidoester benzamidines as potent inhibitors of recombinant human betaII tryptase. X-ray structure driven template modification and exchange of the benzamidine to optimize potency and pharmacokinetic properties gave selective, potent and orally bioavailable 4-(3-aminomethyl phenyl)piperidinyl-1-amides.

PubMed: 15781396
DOI: 10.1016/J.BMC.2005.02.014

実験手法

X-RAY DIFFRACTION (2.2 Å)