2bm2

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (13:44, 13 December 2023) (edit) (undo)
 
(16 intermediate revisions not shown.)
Line 1: Line 1:
-
[[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;" />
 
-
'''HUMAN BETA-II TRYPTASE IN COMPLEX WITH 4-(3-AMINOMETHYL-PHENYL)-PIPERIDIN-1-YL-(5-PHENETHYL- PYRIDIN-3-YL)-METHANONE'''<br />
 
-
==Overview==
+
==human beta-II tryptase in complex with 4-(3-Aminomethyl-phenyl)- piperidin-1-yl-(5-phenethyl- pyridin-3-yl)-methanone==
-
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.
+
<StructureSection load='2bm2' size='340' side='right'caption='[[2bm2]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 +
== Structural highlights ==
 +
<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>
 +
</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>
 +
<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>
 +
<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>
 +
</table>
 +
== Function ==
 +
[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).
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bm/2bm2_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</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].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
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==
+
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>
-
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==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
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://ispc.weizmann.ac.il//pmbin/getpm?pmid=15781396 15781396]
+
</div>
-
[[Category: Homo sapiens]]
+
<div class="pdbe-citations 2bm2" style="background-color:#fffaf0;"></div>
-
[[Category: Single protein]]
+
-
[[Category: Tryptase]]
+
-
[[Category: Aldous, S.]]
+
-
[[Category: Astles, P.]]
+
-
[[Category: Cairns, J.]]
+
-
[[Category: Czekaj, M.]]
+
-
[[Category: Davidson, J.]]
+
-
[[Category: Dupuy, A.]]
+
-
[[Category: Eastwood, P.]]
+
-
[[Category: Engers, D.]]
+
-
[[Category: Fenton, G.]]
+
-
[[Category: Gardyan, M.]]
+
-
[[Category: Giardino, O.]]
+
-
[[Category: Guilloteau, J.P.]]
+
-
[[Category: Harrison, T.]]
+
-
[[Category: Houille, O.]]
+
-
[[Category: Kwong, J.]]
+
-
[[Category: Levell, J.]]
+
-
[[Category: Liang, G.]]
+
-
[[Category: Lim, H.K.]]
+
-
[[Category: Luo, Y.]]
+
-
[[Category: Maignan, S.]]
+
-
[[Category: Mathew, R.]]
+
-
[[Category: Mccarthy, C.]]
+
-
[[Category: Merriman, G.]]
+
-
[[Category: Morley, A.]]
+
-
[[Category: Pauls, H.]]
+
-
[[Category: Pribish, J.]]
+
-
[[Category: Rebello, S.]]
+
-
[[Category: Romano, J.]]
+
-
[[Category: Shen, L.]]
+
-
[[Category: Sides, K.]]
+
-
[[Category: Smith, K.]]
+
-
[[Category: Tsay, J.]]
+
-
[[Category: Wang, J.]]
+
-
[[Category: Watson, S.]]
+
-
[[Category: Whiteley, B.]]
+
-
[[Category: PM2]]
+
-
[[Category: glycoprotein]]
+
-
[[Category: hydrolase]]
+
-
[[Category: polymorphism]]
+
-
[[Category: protease]]
+
-
[[Category: serine protease]]
+
-
[[Category: serine protease inhibitor]]
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:25:43 2008''
+
==See Also==
 +
*[[Tryptase|Tryptase]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Homo sapiens]]
 +
[[Category: Large Structures]]
 +
[[Category: Aldous S]]
 +
[[Category: Astles P]]
 +
[[Category: Cairns J]]
 +
[[Category: Czekaj M]]
 +
[[Category: Davidson J]]
 +
[[Category: Dupuy A]]
 +
[[Category: Eastwood P]]
 +
[[Category: Engers D]]
 +
[[Category: Fenton G]]
 +
[[Category: Gardyan M]]
 +
[[Category: Giardino O]]
 +
[[Category: Guilloteau J-P]]
 +
[[Category: Harrison T]]
 +
[[Category: Houille O]]
 +
[[Category: Kwong J]]
 +
[[Category: Levell J]]
 +
[[Category: Liang G]]
 +
[[Category: Lim H-K]]
 +
[[Category: Luo Y]]
 +
[[Category: Maignan S]]
 +
[[Category: Mathew R]]
 +
[[Category: Mccarthy C]]
 +
[[Category: Merriman G]]
 +
[[Category: Morley A]]
 +
[[Category: Pauls H]]
 +
[[Category: Pribish J]]
 +
[[Category: Rebello S]]
 +
[[Category: Romano J]]
 +
[[Category: Shen L]]
 +
[[Category: Sides K]]
 +
[[Category: Smith K]]
 +
[[Category: Tsay J]]
 +
[[Category: Wang J]]
 +
[[Category: Watson S]]
 +
[[Category: Whiteley B]]

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

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2bm2"
Personal tools