2bm2

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[[Image:2bm2.gif|left|200px]]<br /><applet load="2bm2" size="450" color="white" frame="true" align="right" spinBox="true"
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[[Image:2bm2.gif|left|200px]]<br /><applet load="2bm2" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2bm2, resolution 2.2&Aring;" />
caption="2bm2, resolution 2.2&Aring;" />
'''HUMAN BETA-II TRYPTASE IN COMPLEX WITH 4-(3-AMINOMETHYL-PHENYL)-PIPERIDIN-1-YL-(5-PHENETHYL- PYRIDIN-3-YL)-METHANONE'''<br />
'''HUMAN BETA-II TRYPTASE IN COMPLEX WITH 4-(3-AMINOMETHYL-PHENYL)-PIPERIDIN-1-YL-(5-PHENETHYL- PYRIDIN-3-YL)-METHANONE'''<br />
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==About this Structure==
==About this Structure==
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2BM2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with PM2 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Tryptase Tryptase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.59 3.4.21.59] Known structural/functional Site: <scene name='pdbsite=AC1:Pm2 Binding Site For Chain D'>AC1</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BM2 OCA].
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2BM2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=PM2:'>PM2</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Tryptase Tryptase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.59 3.4.21.59] Known structural/functional Site: <scene name='pdbsite=AC1:Pm2+Binding+Site+For+Chain+D'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BM2 OCA].
==Reference==
==Reference==
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[[Category: serine protease inhibitor]]
[[Category: serine protease inhibitor]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 18:52:00 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:25:43 2008''

Revision as of 08:25, 3 February 2008


2bm2, resolution 2.2Å

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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

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