2BM2

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

Summary for 2BM2

• Entry DOI: 10.2210/pdb2bm2/pdb
• Related: 1A0L 1AAO
• Descriptor: HUMAN BETA2 TRYPTASE, 1-[3-(1-{[5-(2-PHENYLETHYL)PYRIDIN-3-YL]CARBONYL}PIPERIDIN-4-YL)PHENYL]METHANAMINE (3 entities in total)
• Functional Keywords: serine protease inhibitor, glycoprotein, hydrolase, polymorphism, protease, serine protease
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 4
• Total formula weight: 111563.82

Authors

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. (deposition date: 2005-03-09, release date: 2005-03-22, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.2 Å)