|
|
| (One intermediate revision not shown.) |
| Line 3: |
Line 3: |
| | <StructureSection load='2o6x' size='340' side='right'caption='[[2o6x]], [[Resolution|resolution]] 1.40Å' scene=''> | | <StructureSection load='2o6x' size='340' side='right'caption='[[2o6x]], [[Resolution|resolution]] 1.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2o6x]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Fashe Fashe]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O6X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2O6X FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2o6x]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Fasciola_hepatica Fasciola hepatica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O6X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2O6X FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1cjl|1cjl]]</div></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]] 1.4Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CL1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6192 FASHE])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Cathepsin_L Cathepsin L], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.15 3.4.22.15] </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=2o6x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o6x OCA], [https://pdbe.org/2o6x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2o6x RCSB], [https://www.ebi.ac.uk/pdbsum/2o6x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2o6x ProSAT]</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=2o6x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o6x OCA], [https://pdbe.org/2o6x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2o6x RCSB], [https://www.ebi.ac.uk/pdbsum/2o6x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2o6x ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/CATLL_FASHE CATLL_FASHE] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 14: |
Line 14: |
| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/o6/2o6x_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/o6/2o6x_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> |
| Line 35: |
Line 35: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cathepsin L]] | + | [[Category: Fasciola hepatica]] |
| - | [[Category: Fashe]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Brinen, L S]] | + | [[Category: Brinen LS]] |
| - | [[Category: Dalton, J P]] | + | [[Category: Dalton JP]] |
| - | [[Category: Geiger, S]] | + | [[Category: Geiger S]] |
| - | [[Category: Marion, R]] | + | [[Category: Marion R]] |
| - | [[Category: Stack, C M]] | + | [[Category: Stack CM]] |
| - | [[Category: Cysteine protease]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Thiol protease]]
| + | |
| - | [[Category: Zymogen]]
| + | |
| Structural highlights
Function
CATLL_FASHE
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
The helminth parasite Fasciola hepatica secretes cysteine proteases to facilitate tissue invasion, migration, and development within the mammalian host. The major proteases cathepsin L1 (FheCL1) and cathepsin L2 (FheCL2) were recombinantly produced and biochemically characterized. By using site-directed mutagenesis, we show that residues at position 67 and 205, which lie within the S2 pocket of the active site, are critical in determining the substrate and inhibitor specificity. FheCL1 exhibits a broader specificity and a higher substrate turnover rate compared with FheCL2. However, FheCL2 can efficiently cleave substrates with a Pro in the P2 position and degrade collagen within the triple helices at physiological pH, an activity that among cysteine proteases has only been reported for human cathepsin K. The 1.4-A three-dimensional structure of the FheCL1 was determined by x-ray crystallography, and the three-dimensional structure of FheCL2 was constructed via homology-based modeling. Analysis and comparison of these structures and our biochemical data with those of human cathepsins L and K provided an interpretation of the substrate-recognition mechanisms of these major parasite proteases. Furthermore, our studies suggest that a configuration involving residue 67 and the "gatekeeper" residues 157 and 158 situated at the entrance of the active site pocket create a topology that endows FheCL2 with its unusual collagenolytic activity. The emergence of a specialized collagenolytic function in Fasciola likely contributes to the success of this tissue-invasive parasite.
Structural and functional relationships in the virulence-associated cathepsin L proteases of the parasitic liver fluke, Fasciola hepatica.,Stack CM, Caffrey CR, Donnelly SM, Seshaadri A, Lowther J, Tort JF, Collins PR, Robinson MW, Xu W, McKerrow JH, Craik CS, Geiger SR, Marion R, Brinen LS, Dalton JP J Biol Chem. 2008 Apr 11;283(15):9896-908. Epub 2007 Dec 26. PMID:18160404[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Stack CM, Caffrey CR, Donnelly SM, Seshaadri A, Lowther J, Tort JF, Collins PR, Robinson MW, Xu W, McKerrow JH, Craik CS, Geiger SR, Marion R, Brinen LS, Dalton JP. Structural and functional relationships in the virulence-associated cathepsin L proteases of the parasitic liver fluke, Fasciola hepatica. J Biol Chem. 2008 Apr 11;283(15):9896-908. Epub 2007 Dec 26. PMID:18160404 doi:10.1074/jbc.M708521200
|
