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| | ==ECOTIN Y69F, D70P BOUND TO D102N TRYPSIN== | | ==ECOTIN Y69F, D70P BOUND TO D102N TRYPSIN== |
| - | <StructureSection load='1ezu' size='340' side='right' caption='[[1ezu]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='1ezu' size='340' side='right'caption='[[1ezu]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1ezu]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EZU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1EZU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1ezu]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EZU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EZU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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">[[1azz|1azz]], [[1ecy|1ecy]], [[1ecz|1ecz]], [[1slu|1slu]], [[1slv|1slv]], [[1slw|1slw]], [[1slx|1slx]], [[1ezs|1ezs]]</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=1ezu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ezu OCA], [https://pdbe.org/1ezu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ezu RCSB], [https://www.ebi.ac.uk/pdbsum/1ezu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ezu 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=1ezu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ezu OCA], [http://pdbe.org/1ezu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ezu RCSB], [http://www.ebi.ac.uk/pdbsum/1ezu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ezu ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ECOT_ECOLI ECOT_ECOLI]] General inhibitor of pancreatic serine proteases: inhibits chymotrypsin, trypsin, elastases, factor X, kallikrein as well as a variety of other proteases. The strength of inhibition does not appear to be correlated with a particular protease specificity.[HAMAP-Rule:MF_00706] | + | [https://www.uniprot.org/uniprot/ECOT_ECOLI ECOT_ECOLI] General inhibitor of pancreatic serine proteases: inhibits chymotrypsin, trypsin, elastases, factor X, kallikrein as well as a variety of other proteases. The strength of inhibition does not appear to be correlated with a particular protease specificity.[HAMAP-Rule:MF_00706] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ez/1ezu_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ez/1ezu_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | ==See Also== | | ==See Also== |
| | *[[Ecotin|Ecotin]] | | *[[Ecotin|Ecotin]] |
| - | *[[Trypsin|Trypsin]] | + | *[[Trypsin 3D structures|Trypsin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Trypsin]] | + | [[Category: Escherichia coli]] |
| - | [[Category: Craik, C S]] | + | [[Category: Large Structures]] |
| - | [[Category: Fletterick, R J]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Gillmor, S A]] | + | [[Category: Craik CS]] |
| - | [[Category: Takeuchi, T]] | + | [[Category: Fletterick RJ]] |
| - | [[Category: Yang, S Q]] | + | [[Category: Gillmor SA]] |
| - | [[Category: Hydrolase-inhibitor complex]] | + | [[Category: Takeuchi T]] |
| - | [[Category: Macromolecular complex]] | + | [[Category: Yang SQ]] |
| - | [[Category: Protease inhibitor]]
| + | |
| - | [[Category: Protein-protein interaction]]
| + | |
| Structural highlights
Function
ECOT_ECOLI General inhibitor of pancreatic serine proteases: inhibits chymotrypsin, trypsin, elastases, factor X, kallikrein as well as a variety of other proteases. The strength of inhibition does not appear to be correlated with a particular protease specificity.[HAMAP-Rule:MF_00706]
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
Ecotin is a dimeric serine protease inhibitor from Escherichia coli which binds proteases to form a hetero-tetramer with three distinct interfaces: an ecotin-ecotin dimer interface, a larger primary ecotin-protease interface, and a smaller secondary ecotin-protease interface. The contributions of these interfaces to binding and inhibition are unequal. To investigate the contribution and adaptability of each interface, we have solved the structure of two mutant ecotin-trypsin complexes and compared them to the structure of the previously determined wild-type ecotin-trypsin complex. Wild-type ecotin has an affinity of 1 nM for trypsin, while the optimized mutant, ecotin Y69F, D70P, which was found using phage display technologies, inhibits rat trypsin with a K(i) value of 0.08 nM. Ecotin 67-70A, M84R which has four alanine substitutions in the ecotin-trypsin secondary binding site, along with the M84R mutation at the primary site, has a K(i) value against rat trypsin of 0.2 nM. The structure of the ecotin Y69F, D70P-trypsin complex shows minor structural changes in the ecotin-trypsin tetramer. The structure of the ecotin 67-70A, M84R mutant bound to trypsin shows large deviations in the tertiary and quaternary structure of the complex. The trypsin structure shows no significant changes, but the conformation of several loop regions of ecotin are altered, resulting in the secondary site releasing its hold on trypsin. The structure of several regions previously considered to be rigid is also significantly modified. The inherent flexibility of ecotin allows it to accommodate these mutations and still maintain tight binding through the compromises of the protein-protein interfaces in the ecotin-trypsin tetramer. A comparison with two recently described ecotin-like genes from other bacteria suggests that these structural and functional features are conserved in otherwise distant bacterial lineages.
Compromise and accommodation in ecotin, a dimeric macromolecular inhibitor of serine proteases.,Gillmor SA, Takeuchi T, Yang SQ, Craik CS, Fletterick RJ J Mol Biol. 2000 Jun 16;299(4):993-1003. PMID:10843853[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gillmor SA, Takeuchi T, Yang SQ, Craik CS, Fletterick RJ. Compromise and accommodation in ecotin, a dimeric macromolecular inhibitor of serine proteases. J Mol Biol. 2000 Jun 16;299(4):993-1003. PMID:10843853 doi:10.1006/jmbi.2000.3812
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