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| | ==Structural Basis for Dual-inhibition Mechanism of a Non-classical Kazal-type Serine Protease Inhibitor from Horseshoe Crab in Complex with Subtilisin== | | ==Structural Basis for Dual-inhibition Mechanism of a Non-classical Kazal-type Serine Protease Inhibitor from Horseshoe Crab in Complex with Subtilisin== |
| - | <StructureSection load='3qtl' size='340' side='right' caption='[[3qtl]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='3qtl' size='340' side='right'caption='[[3qtl]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3qtl]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacillus_licheniformis Bacillus licheniformis] and [http://en.wikipedia.org/wiki/Carcinoscorpius_rotundicauda Carcinoscorpius rotundicauda]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QTL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QTL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3qtl]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_licheniformis Bacillus licheniformis] and [https://en.wikipedia.org/wiki/Carcinoscorpius_rotundicauda Carcinoscorpius rotundicauda]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QTL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QTL FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">aprE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1402 Bacillus licheniformis]), SPI-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6848 Carcinoscorpius rotundicauda])</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]] 2.6Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Subtilisin Subtilisin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.62 3.4.21.62] </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=3qtl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qtl OCA], [https://pdbe.org/3qtl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qtl RCSB], [https://www.ebi.ac.uk/pdbsum/3qtl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qtl ProSAT]</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=3qtl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qtl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qtl RCSB], [http://www.ebi.ac.uk/pdbsum/3qtl PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q6PNN5_BACLI Q6PNN5_BACLI] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3qtl" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | [[Category: Bacillus licheniformis]] | | [[Category: Bacillus licheniformis]] |
| | [[Category: Carcinoscorpius rotundicauda]] | | [[Category: Carcinoscorpius rotundicauda]] |
| - | [[Category: Subtilisin]] | + | [[Category: Large Structures]] |
| - | [[Category: Shenoy, R T]] | + | [[Category: Shenoy RT]] |
| - | [[Category: Sivaraman, J]] | + | [[Category: Sivaraman J]] |
| - | [[Category: Hydrolase inhibitor]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
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| - | [[Category: Serine protease -kazal type serine protease inhibitor complex]]
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| Structural highlights
Function
Q6PNN5_BACLI
Publication Abstract from PubMed
Serine proteases play a crucial role in host-pathogen interactions. In the innate immune system of invertebrates, multi-domain protease inhibitors are important for the regulation of host-pathogen interactions and antimicrobial activities. Serine protease inhibitors, 9.3-kDa CrSPI isoforms 1 and 2, have been identified from the hepatopancreas of the horseshoe crab, Carcinoscorpius rotundicauda. The CrSPIs were biochemically active, especially CrSPI-1, which potently inhibited subtilisin (Ki = 1.43 nM). CrSPI has been grouped with the non-classical Kazal-type inhibitors due to its unusual cysteine distribution. Here we report the crystal structure of CrSPI-1 in complex with subtilisin at 2.6 A resolution and the results of biophysical interaction studies. The CrSPI-1 molecule has two domains arranged in an extended conformation. These two domains act as heads that independently interact with two separate subtilisin molecules, resulting in the inhibition of subtilisin activity at a ratio of 1:2 (inhibitor to protease). Each subtilisin molecule interacts with the reactive site loop from each domain of CrSPI-1 through a standard canonical binding mode and forms a single ternary complex. In addition, we propose the substrate preferences of each domain of CrSPI-1. Domain 2 is specific towards the bacterial protease subtilisin, while domain 1 is likely to interact with the host protease, Furin. Elucidation of the structure of the CrSPI-1: subtilisin (1ratio2) ternary complex increases our understanding of host-pathogen interactions in the innate immune system at the molecular level and provides new strategies for immunomodulation.
Structural basis for dual-inhibition mechanism of a non-classical kazal-type serine protease inhibitor from horseshoe crab in complex with subtilisin.,Shenoy RT, Thangamani S, Velazquez-Campoy A, Ho B, Ding JL, Sivaraman J PLoS One. 2011 Apr 26;6(4):e18838. PMID:21541315[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Shenoy RT, Thangamani S, Velazquez-Campoy A, Ho B, Ding JL, Sivaraman J. Structural basis for dual-inhibition mechanism of a non-classical kazal-type serine protease inhibitor from horseshoe crab in complex with subtilisin. PLoS One. 2011 Apr 26;6(4):e18838. PMID:21541315 doi:10.1371/journal.pone.0018838
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