1nc6: Difference between revisions

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<StructureSection load='1nc6' size='340' side='right'caption='[[1nc6]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
<StructureSection load='1nc6' size='340' side='right'caption='[[1nc6]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1nc6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NC6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NC6 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1nc6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NC6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NC6 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ABB:(2S,4R)-1-ACETYL-N-[(1S)-4-[(AMINOIMINOMETHYL)AMINO]-1-(2-BENZOTHIAZOLYLCARBONYL)BUTYL]-4-HYDROXY-2-PYRROLIDINECARBOXAMIDE'>ABB</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Trypsin Trypsin], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.4 3.4.21.4] </span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ABB:(2S,4R)-1-ACETYL-N-[(1S)-4-[(AMINOIMINOMETHYL)AMINO]-1-(2-BENZOTHIAZOLYLCARBONYL)BUTYL]-4-HYDROXY-2-PYRROLIDINECARBOXAMIDE'>ABB</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1nc6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nc6 OCA], [https://pdbe.org/1nc6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nc6 RCSB], [https://www.ebi.ac.uk/pdbsum/1nc6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nc6 ProSAT]</span></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=1nc6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nc6 OCA], [https://pdbe.org/1nc6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nc6 RCSB], [https://www.ebi.ac.uk/pdbsum/1nc6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nc6 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TRY1_BOVIN TRY1_BOVIN]
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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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=1nc6 ConSurf].
</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=1nc6 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Inhibitors of human mast cell tryptase (EC 3.4.21.59) have therapeutic potential for treating allergic or inflammatory disorders. We have investigated transition-state mimetics possessing a heterocycle-activated ketone group and identified in particular benzothiazole ketone (2S)-6 (RWJ-56423) as a potent, reversible, low-molecular-weight tryptase inhibitor with a K(i) value of 10 nM. A single-crystal X-ray analysis of the sulfate salt of (2S)-6 confirmed the stereochemistry. Analogues 12 and 15-17 are also potent tryptase inhibitors. Although RWJ-56423 potently inhibits trypsin (K(i) = 8.1 nM), it is selective vs other serine proteases, such as kallikrein, plasmin, and thrombin. We obtained an X-ray structure of (2S)-6 complexed with bovine trypsin (1.9-A resolution), which depicts inter alia a hemiketal involving Ser-189, and hydrogen bonds with His-57 and Gln-192. Aerosol administration of 6 (2R,2S; RWJ-58643) to allergic sheep effectively antagonized antigen-induced asthmatic responses, with 70-75% blockade of the early response and complete ablation of the late response and airway hyperresponsiveness.
Potent, small-molecule inhibitors of human mast cell tryptase. Antiasthmatic action of a dipeptide-based transition-state analogue containing a benzothiazole ketone.,Costanzo MJ, Yabut SC, Almond HR Jr, Andrade-Gordon P, Corcoran TW, De Garavilla L, Kauffman JA, Abraham WM, Recacha R, Chattopadhyay D, Maryanoff BE J Med Chem. 2003 Aug 28;46(18):3865-76. PMID:12930148<ref>PMID:12930148</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1nc6" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Trypsin 3D structures|Trypsin 3D structures]]
*[[Trypsin 3D structures|Trypsin 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Bovin]]
[[Category: Bos taurus]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Trypsin]]
[[Category: Abraham WM]]
[[Category: Abraham, W M]]
[[Category: Almond Jr HR]]
[[Category: Almond, H R]]
[[Category: Andrade-Gordon P]]
[[Category: Andrade-Gordon, P]]
[[Category: Chattopadhyay D]]
[[Category: Chattopadhyay, D]]
[[Category: Corcoran TW]]
[[Category: Corcoran, T W]]
[[Category: Costanzo MJ]]
[[Category: Costanzo, M J]]
[[Category: Kauffman JA]]
[[Category: Garavilla, L de]]
[[Category: Maryanoff BE]]
[[Category: Kauffman, J A]]
[[Category: Recacha R]]
[[Category: Maryanoff, B E]]
[[Category: Yabut SC]]
[[Category: Recacha, R]]
[[Category: De Garavilla L]]
[[Category: Yabut, S C]]
[[Category: Hydrolase]]
[[Category: Protein-inhibitor complex]]

Revision as of 08:47, 10 April 2024

Potent, small molecule inhibitors of human mast cell tryptase. Anti-asthmatic action of a dipeptide-based transition state analogue containing benzothiazole ketone

1nc6, resolution 1.90Å

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