View source for 2uuy


==Structure of a tick tryptase inhibitor in complex with bovine trypsin==
<StructureSection load='2uuy' size='340' side='right'caption='[[2uuy]], [[Resolution|resolution]] 1.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2uuy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Rhipicephalus_appendiculatus Rhipicephalus appendiculatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UUY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2UUY FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2uux|2uux]], [[1aq7|1aq7]], [[1auj|1auj]], [[1az8|1az8]], [[1bju|1bju]], [[1bjv|1bjv]], [[1btp|1btp]], [[1btw|1btw]], [[1btx|1btx]], [[1bty|1bty]], [[1btz|1btz]], [[1c1n|1c1n]], [[1c1o|1c1o]], [[1c1p|1c1p]], [[1c1q|1c1q]], [[1c1r|1c1r]], [[1c1s|1c1s]], [[1c1t|1c1t]], [[1c2d|1c2d]], [[1c2e|1c2e]], [[1c2f|1c2f]], [[1c2g|1c2g]], [[1c2h|1c2h]], [[1c2i|1c2i]], [[1c2j|1c2j]], [[1c2k|1c2k]], [[1c2l|1c2l]], [[1c2m|1c2m]], [[1c5p|1c5p]], [[1c5q|1c5q]], [[1c5r|1c5r]], [[1c5s|1c5s]], [[1c5t|1c5t]], [[1c5u|1c5u]], [[1c5v|1c5v]], [[1c9t|1c9t]], [[1ce5|1ce5]], [[1cu7|1cu7]], [[1cu8|1cu8]], [[1cu9|1cu9]], [[1d6r|1d6r]], [[1eb2|1eb2]], [[1ejm|1ejm]], [[1ezx|1ezx]], [[1f0t|1f0t]], [[1f0u|1f0u]], [[1f2s|1f2s]], [[1g36|1g36]], [[1g3b|1g3b]], [[1g3c|1g3c]], [[1g3d|1g3d]], [[1g3e|1g3e]], [[1g9i|1g9i]], [[1gbt|1gbt]], [[1ghz|1ghz]], [[1gi0|1gi0]], [[1gi1|1gi1]], [[1gi2|1gi2]], [[1gi3|1gi3]], [[1gi4|1gi4]], [[1gi5|1gi5]], [[1gi6|1gi6]], [[1gj6|1gj6]], [[1hj9|1hj9]], [[1j8a|1j8a]], [[1jir|1jir]], [[1jrs|1jrs]], [[1jrt|1jrt]], [[1k1i|1k1i]], [[1k1j|1k1j]], [[1k1l|1k1l]], [[1k1m|1k1m]], [[1k1n|1k1n]], [[1k1o|1k1o]], [[1k1p|1k1p]], [[1lqe|1lqe]], [[1max|1max]], [[1may|1may]], [[1mts|1mts]], [[1mtu|1mtu]], [[1mtv|1mtv]], [[1mtw|1mtw]], [[1n6x|1n6x]], [[1n6y|1n6y]], [[1nc6|1nc6]], [[1ntp|1ntp]], [[1o2h|1o2h]], [[1o2i|1o2i]], [[1o2j|1o2j]], [[1o2k|1o2k]], [[1o2l|1o2l]], [[1o2m|1o2m]], [[1o2n|1o2n]], [[1o2o|1o2o]], [[1o2p|1o2p]], [[1o2q|1o2q]], [[1o2r|1o2r]], [[1o2s|1o2s]], [[1o2t|1o2t]], [[1o2u|1o2u]], [[1o2v|1o2v]], [[1o2w|1o2w]], [[1o2x|1o2x]], [[1o2y|1o2y]], [[1o2z|1o2z]], [[1o30|1o30]], [[1o31|1o31]], [[1o32|1o32]], [[1o33|1o33]], [[1o34|1o34]], [[1o35|1o35]], [[1o36|1o36]], [[1o37|1o37]], [[1o38|1o38]], [[1o39|1o39]], [[1o3a|1o3a]], [[1o3b|1o3b]], [[1o3c|1o3c]], [[1o3d|1o3d]], [[1o3e|1o3e]], [[1o3f|1o3f]], [[1o3g|1o3g]], [[1o3h|1o3h]], [[1o3i|1o3i]], [[1o3j|1o3j]], [[1o3k|1o3k]], [[1o3l|1o3l]], [[1o3m|1o3m]], [[1o3n|1o3n]], [[1o3o|1o3o]], [[1oph|1oph]], [[1ox1|1ox1]], [[1oyq|1oyq]], [[1p2i|1p2i]], [[1p2j|1p2j]], [[1p2k|1p2k]], [[1ppc|1ppc]], [[1ppe|1ppe]], [[1pph|1pph]], [[1qa0|1qa0]], [[1qb1|1qb1]], [[1qb6|1qb6]], [[1qb9|1qb9]], [[1qbn|1qbn]], [[1qbo|1qbo]], [[1qcp|1qcp]], [[1ql7|1ql7]], [[1ql8|1ql8]], [[1rxp|1rxp]], [[1s0q|1s0q]], [[1s0r|1s0r]], [[1sbw|1sbw]], [[1sfi|1sfi]], [[1smf|1smf]], [[1tab|1tab]], [[1taw|1taw]], [[1tgb|1tgb]], [[1tgc|1tgc]], [[1tgn|1tgn]], [[1tgs|1tgs]], [[1tgt|1tgt]], [[1tio|1tio]], [[1tld|1tld]], [[1tng|1tng]], [[1tnh|1tnh]], [[1tni|1tni]], [[1tnj|1tnj]], [[1tnk|1tnk]], [[1tnl|1tnl]], [[1tpa|1tpa]], [[1tpo|1tpo]], [[1tpp|1tpp]], [[1tps|1tps]], [[1tx7|1tx7]], [[1tx8|1tx8]], [[1tyn|1tyn]], [[1utn|1utn]], [[1uto|1uto]], [[1utp|1utp]], [[1utq|1utq]], [[1v2j|1v2j]], [[1v2k|1v2k]], [[1v2l|1v2l]], [[1v2m|1v2m]], [[1v2n|1v2n]], [[1v2o|1v2o]], [[1v2p|1v2p]], [[1v2q|1v2q]], [[1v2r|1v2r]], [[1v2s|1v2s]], [[1v2t|1v2t]], [[1v2u|1v2u]], [[1v2v|1v2v]], [[1v2w|1v2w]], [[1xuf|1xuf]], [[1xug|1xug]], [[1xuh|1xuh]], [[1xui|1xui]], [[1xuj|1xuj]], [[1xuk|1xuk]], [[1y3u|1y3u]], [[1y3v|1y3v]], [[1y3w|1y3w]], [[1y3x|1y3x]], [[1y3y|1y3y]], [[1y59|1y59]], [[1y5a|1y5a]], [[1y5b|1y5b]], [[1y5u|1y5u]], [[1yp9|1yp9]], [[1yyy|1yyy]], [[1zr0|1zr0]], [[1zzz|1zzz]], [[2a7h|2a7h]], [[2ah4|2ah4]], [[2ayw|2ayw]], [[2blv|2blv]], [[2blw|2blw]], [[2btc|2btc]], [[2by5|2by5]], [[2by6|2by6]], [[2by7|2by7]], [[2by8|2by8]], [[2by9|2by9]], [[2bya|2bya]], [[2bza|2bza]], [[2cmy|2cmy]], [[2fi3|2fi3]], [[2fi4|2fi4]], [[2fi5|2fi5]], [[2ftl|2ftl]], [[2ftm|2ftm]], [[2fx4|2fx4]], [[2fx6|2fx6]], [[2j9n|2j9n]], [[2ptc|2ptc]], [[2ptn|2ptn]], [[2tga|2tga]], [[2tgd|2tgd]], [[2tgp|2tgp]], [[2tgt|2tgt]], [[2tio|2tio]], [[2tld|2tld]], [[2tpi|2tpi]], [[3btd|3btd]], [[3bte|3bte]], [[3btf|3btf]], [[3btg|3btg]], [[3bth|3bth]], [[3btk|3btk]], [[3btm|3btm]], [[3btq|3btq]], [[3btt|3btt]], [[3btw|3btw]], [[3ptb|3ptb]], [[3ptn|3ptn]], [[3tpi|3tpi]], [[4tpi|4tpi]], [[5ptp|5ptp]]</div></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://proteopedia.org/fgij/fg.htm?mol=2uuy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uuy OCA], [http://pdbe.org/2uuy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2uuy RCSB], [http://www.ebi.ac.uk/pdbsum/2uuy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2uuy ProSAT]</span></td></tr>
</table>
== 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/uu/2uuy_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=2uuy ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
TdPI, a tick salivary gland product related to Kunitz/BPTI proteins is a potent inhibitor of human beta-tryptase. Kinetic assays suggest that three of the four catalytic sites of tryptase are blocked by TdPI, and that the inhibition of one of these involves a peptide flanking the Kunitz head. In the course of the inhibition, tryptase cleaves TdPI at several positions. Crystal structures of the TdPI head, on its own and in complex with trypsin, reveal features that are not found in classical Kunitz/BPTI proteins and suggest the mode of interaction with tryptase. The loop of TdPI connecting the beta-sheet with the C-terminal alpha-helix is shortened, the disulphide-bridge pattern altered and N and C termini separated to produce a highly pointed molecule capable of penetrating the cramped active sites of tryptase. TdPI accumulates in the cytosolic granules of mast cells, presumably suppressing inflammation in the host animal's skin by tryptase inhibition.

A tick protein with a modified Kunitz fold inhibits human tryptase.,Paesen GC, Siebold C, Harlos K, Peacey MF, Nuttall PA, Stuart DI J Mol Biol. 2007 May 11;368(4):1172-86. Epub 2007 Mar 14. PMID:17391695<ref>PMID:17391695</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2uuy" style="background-color:#fffaf0;"></div>

==See Also==
*[[Trypsin 3D structures|Trypsin 3D structures]]
*[[Tryptase inhibitor|Tryptase inhibitor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Large Structures]]
[[Category: Rhipicephalus appendiculatus]]
[[Category: Trypsin]]
[[Category: Harlos, K]]
[[Category: Nuttall, P A]]
[[Category: Paesen, G C]]
[[Category: Peacey, M F]]
[[Category: Siebold, C]]
[[Category: Stuart, D I]]
[[Category: Calcium]]
[[Category: Digestion]]
[[Category: Hydrolase]]
[[Category: Metal-binding]]
[[Category: Protease]]
[[Category: Serine protease]]
[[Category: Tryptase inhibitor]]
[[Category: Zymogen]]