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| | <StructureSection load='3i29' size='340' side='right'caption='[[3i29]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='3i29' size='340' side='right'caption='[[3i29]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3i29]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin] and [http://en.wikipedia.org/wiki/Dolichos_tetragonolobus Dolichos tetragonolobus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3I29 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3I29 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3i29]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Psophocarpus_tetragonolobus Psophocarpus tetragonolobus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3I29 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3I29 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></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]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2qyi|2qyi]], [[3i2a|3i2a]], [[3i2x|3i2x]]</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></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'>[https://proteopedia.org/fgij/fg.htm?mol=3i29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i29 OCA], [https://pdbe.org/3i29 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3i29 RCSB], [https://www.ebi.ac.uk/pdbsum/3i29 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3i29 ProSAT]</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=3i29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i29 OCA], [http://pdbe.org/3i29 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3i29 RCSB], [http://www.ebi.ac.uk/pdbsum/3i29 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3i29 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ICW3_PSOTE ICW3_PSOTE]] Inhibits alpha-chymotrypsin at the molar ratio of 1:2 in state of 1:1. | + | [https://www.uniprot.org/uniprot/ICW3_PSOTE ICW3_PSOTE] Inhibits alpha-chymotrypsin at the molar ratio of 1:2 in state of 1:1. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bovin]] | + | [[Category: Bos taurus]] |
| - | [[Category: Dolichos tetragonolobus]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Trypsin]] | + | [[Category: Psophocarpus tetragonolobus]] |
| - | [[Category: Dasgupta, J]] | + | [[Category: Dasgupta J]] |
| - | [[Category: Dattagupta, J K]] | + | [[Category: Dattagupta JK]] |
| - | [[Category: Khamrui, S]] | + | [[Category: Khamrui S]] |
| - | [[Category: Majumder, S]] | + | [[Category: Majumder S]] |
| - | [[Category: Sen, U]] | + | [[Category: Sen U]] |
| - | [[Category: Bovine trypsin]]
| + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Digestion]]
| + | |
| - | [[Category: Disulfide bond]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: P1 and p2 mutant]]
| + | |
| - | [[Category: Protease]]
| + | |
| - | [[Category: Protease inhibitor]]
| + | |
| - | [[Category: Secreted]]
| + | |
| - | [[Category: Serine protease]]
| + | |
| - | [[Category: Serine protease inhibitor]]
| + | |
| - | [[Category: Trypsin inhibitor]]
| + | |
| - | [[Category: Zymogen]]
| + | |
| Structural highlights
Function
ICW3_PSOTE Inhibits alpha-chymotrypsin at the molar ratio of 1:2 in state of 1:1.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Canonical serine protease inhibitors interact with cognate enzymes through the P3-P2' region of the inhibitory loop while its scaffold hardly makes any contact. Neighboring scaffolding residues like Arginines or Asparagine shape-up the inhibitory loop and favor the resynthesis of cleaved scissile bond. However, role of remote scaffolding residues, which are not involved in religation, was not properly explored. Crystal structures of two engineered winged bean chymotrypsin inhibitor (WCI) complexed with Bovine trypsin (BPT) namely L65R-WCI:BPT and F64Y/L65R-WCI:BPT show that the inhibitory loop of these engineered inhibitors are recognized and rigidified properly at the enzyme active site like other strong trypsin inhibitors. Chimeric protein ETI(L)-WCI(S), having a loop of Erythrina caffra Trypsin Inhibitor, ETI on the scaffold of WCI, was previously shown to behave like substrate. Non-canonical structure of the inhibitory loop and its flexibility are attributed to the presence of smaller scaffolding residues which cannot act as barrier to the inhibitory loop like in ETI. Double mutant A76R/L115Y-(ETI(L)-WCI(S)), where the barrier is reintroduced on ETI(L)-WCI(S), shows regaining of inhibitory activity. The structure of A76R/L115Y-(ETI(L)-WCI(S)) along with L65R-WCI:BPT and F64Y/L65R-WCI:BPT demonstrate here that the lost canonical conformation of the inhibitory loop is fully restored and loop flexibility is dramatically reduced. Therefore, residues at the inhibitory loop interact with the enzyme playing the primary role in recognition and binding but scaffolding residues having no direct interaction with the enzyme are crucial for rigidification event and the inhibitory potency. B-factor analysis indicates that the amount of inhibitory loop rigidification varies between different inhibitor families.
Role of remote scaffolding residues in the inhibitory loop pre-organization, flexibility, rigidification and enzyme inhibition of serine protease inhibitors.,Majumder S, Khamrui S, Dasgupta J, Dattagupta JK, Sen U Biochim Biophys Acta. 2012 Jul;1824(7):882-90. doi: 10.1016/j.bbapap.2012.04.009., Epub 2012 May 1. PMID:22709512[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Majumder S, Khamrui S, Dasgupta J, Dattagupta JK, Sen U. Role of remote scaffolding residues in the inhibitory loop pre-organization, flexibility, rigidification and enzyme inhibition of serine protease inhibitors. Biochim Biophys Acta. 2012 Jul;1824(7):882-90. doi: 10.1016/j.bbapap.2012.04.009., Epub 2012 May 1. PMID:22709512 doi:http://dx.doi.org/10.1016/j.bbapap.2012.04.009
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