2bm2
From Proteopedia
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HUMAN BETA-II TRYPTASE IN COMPLEX WITH 4-(3-AMINOMETHYL-PHENYL)-PIPERIDIN-1-YL-(5-PHENETHYL- PYRIDIN-3-YL)-METHANONE
Overview
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.
About this Structure
2BM2 is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Tryptase, with EC number 3.4.21.59 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Structure based design of 4-(3-aminomethylphenyl)piperidinyl-1-amides: novel, potent, selective, and orally bioavailable inhibitors of betaII tryptase., Levell J, Astles P, Eastwood P, Cairns J, Houille O, Aldous S, Merriman G, Whiteley B, Pribish J, Czekaj M, Liang G, Maignan S, Guilloteau JP, 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 HK, Smith K, Pauls H, Bioorg Med Chem. 2005 Apr 15;13(8):2859-72. PMID:15781396
Page seeded by OCA on Thu Feb 21 16:39:14 2008
Categories: Homo sapiens | Single protein | Tryptase | Aldous, S. | Astles, P. | Cairns, J. | Czekaj, M. | Davidson, J. | Dupuy, A. | Eastwood, P. | Engers, D. | Fenton, G. | Gardyan, M. | Giardino, O. | Guilloteau, J P. | Harrison, T. | Houille, O. | Kwong, J. | Levell, J. | Liang, G. | Lim, H K. | Luo, Y. | Maignan, S. | Mathew, R. | Mccarthy, C. | Merriman, G. | Morley, A. | Pauls, H. | Pribish, J. | Rebello, S. | Romano, J. | Shen, L. | Sides, K. | Smith, K. | Tsay, J. | Wang, J. | Watson, S. | Whiteley, B. | PM2 | Glycoprotein | Hydrolase | Polymorphism | Protease | Serine protease | Serine protease inhibitor
