2bm2

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[[Image:2bm2.gif|left|200px]]
 
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{{Structure
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==human beta-II tryptase in complex with 4-(3-Aminomethyl-phenyl)- piperidin-1-yl-(5-phenethyl- pyridin-3-yl)-methanone==
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|PDB= 2bm2 |SIZE=350|CAPTION= <scene name='initialview01'>2bm2</scene>, resolution 2.2&Aring;
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<StructureSection load='2bm2' size='340' side='right'caption='[[2bm2]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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|SITE= <scene name='pdbsite=AC1:Pm2+Binding+Site+For+Chain+D'>AC1</scene>
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=PM2:1-[3-(1-{[5-(2-PHENYLETHYL)PYRIDIN-3-YL]CARBONYL}PIPERIDIN-4-YL)PHENYL]METHANAMINE'>PM2</scene>
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<table><tr><td colspan='2'>[[2bm2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BM2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BM2 FirstGlance]. <br>
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|ACTIVITY= <span class='plainlinks'>[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] </span>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
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|GENE=
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PM2:1-[3-(1-{[5-(2-PHENYLETHYL)PYRIDIN-3-YL]CARBONYL}PIPERIDIN-4-YL)PHENYL]METHANAMINE'>PM2</scene></td></tr>
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|DOMAIN=
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2bm2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bm2 OCA], [https://pdbe.org/2bm2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bm2 RCSB], [https://www.ebi.ac.uk/pdbsum/2bm2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bm2 ProSAT]</span></td></tr>
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|RELATEDENTRY=
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2bm2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bm2 OCA], [http://www.ebi.ac.uk/pdbsum/2bm2 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2bm2 RCSB]</span>
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== Function ==
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}}
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[https://www.uniprot.org/uniprot/TRYB2_HUMAN TRYB2_HUMAN] Tryptase is the major neutral protease present in mast cells and is secreted upon the coupled activation-degranulation response of this cell type. Has an immunoprotective role during bacterial infection. Required to efficiently combat K.pneumoniae infection (By similarity).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bm/2bm2_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2bm2 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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'''HUMAN BETA-II TRYPTASE IN COMPLEX WITH 4-(3-AMINOMETHYL-PHENYL)-PIPERIDIN-1-YL-(5-PHENETHYL- PYRIDIN-3-YL)-METHANONE'''
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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<ref>PMID:15781396</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2bm2" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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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.
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*[[Tryptase|Tryptase]]
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== References ==
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==About this Structure==
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<references/>
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2BM2 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BM2 OCA].
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__TOC__
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</StructureSection>
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==Reference==
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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:[http://www.ncbi.nlm.nih.gov/pubmed/15781396 15781396]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Tryptase]]
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[[Category: Aldous S]]
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[[Category: Aldous, S.]]
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[[Category: Astles P]]
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[[Category: Astles, P.]]
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[[Category: Cairns J]]
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[[Category: Cairns, J.]]
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[[Category: Czekaj M]]
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[[Category: Czekaj, M.]]
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[[Category: Davidson J]]
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[[Category: Davidson, J.]]
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[[Category: Dupuy A]]
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[[Category: Dupuy, A.]]
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[[Category: Eastwood P]]
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[[Category: Eastwood, P.]]
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[[Category: Engers D]]
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[[Category: Engers, D.]]
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[[Category: Fenton G]]
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[[Category: Fenton, G.]]
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[[Category: Gardyan M]]
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[[Category: Gardyan, M.]]
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[[Category: Giardino O]]
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[[Category: Giardino, O.]]
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[[Category: Guilloteau J-P]]
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[[Category: Guilloteau, J P.]]
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[[Category: Harrison T]]
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[[Category: Harrison, T.]]
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[[Category: Houille O]]
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[[Category: Houille, O.]]
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[[Category: Kwong J]]
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[[Category: Kwong, J.]]
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[[Category: Levell J]]
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[[Category: Levell, J.]]
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[[Category: Liang G]]
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[[Category: Liang, G.]]
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[[Category: Lim H-K]]
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[[Category: Lim, H K.]]
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[[Category: Luo Y]]
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[[Category: Luo, Y.]]
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[[Category: Maignan S]]
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[[Category: Maignan, S.]]
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[[Category: Mathew R]]
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[[Category: Mathew, R.]]
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[[Category: Mccarthy C]]
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[[Category: Mccarthy, C.]]
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[[Category: Merriman G]]
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[[Category: Merriman, G.]]
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[[Category: Morley A]]
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[[Category: Morley, A.]]
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[[Category: Pauls H]]
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[[Category: Pauls, H.]]
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[[Category: Pribish J]]
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[[Category: Pribish, J.]]
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[[Category: Rebello S]]
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[[Category: Rebello, S.]]
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[[Category: Romano J]]
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[[Category: Romano, J.]]
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[[Category: Shen L]]
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[[Category: Shen, L.]]
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[[Category: Sides K]]
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[[Category: Sides, K.]]
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[[Category: Smith K]]
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[[Category: Smith, K.]]
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[[Category: Tsay J]]
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[[Category: Tsay, J.]]
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[[Category: Wang J]]
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[[Category: Wang, J.]]
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[[Category: Watson S]]
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[[Category: Watson, S.]]
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[[Category: Whiteley B]]
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[[Category: Whiteley, B.]]
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[[Category: glycoprotein]]
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[[Category: hydrolase]]
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[[Category: polymorphism]]
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[[Category: protease]]
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[[Category: serine protease]]
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[[Category: serine protease inhibitor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:08:23 2008''
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Current revision

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

PDB ID 2bm2

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