1nc6

<StructureSection load='1nc6' size='340' side='right' caption='[[1nc6]], [[Resolution|resolution]] 1.90&Aring;' scene=''>

<table><tr><td colspan='2'>[[1nc6]] is a 1 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1NC6 FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Trypsin Trypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.4 3.4.21.4] </span></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1nc6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nc6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1nc6 RCSB], [http://www.ebi.ac.uk/pdbsum/1nc6 PDBsum]</span></td></tr>

<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nc/1nc6_consurf.spt"</scriptWhenChecked>

</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/chain_selection.php?pdb_ID=2ata ConSurf].

<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>

*[[Trypsin|Trypsin]]

[[Category: Trypsin]]

[[Category: Abraham, W M]]

[[Category: Almond, H R]]

[[Category: Andrade-Gordon, P]]

[[Category: Chattopadhyay, D]]

[[Category: Corcoran, T W]]

[[Category: Costanzo, M J]]

[[Category: Garavilla, L de]]

[[Category: Kauffman, J A]]

[[Category: Maryanoff, B E]]

[[Category: Recacha, R]]

[[Category: Yabut, S C]]

[[Category: Hydrolase]]

[[Category: Protein-inhibitor complex]]