3cbk: Difference between revisions
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< | ==chagasin-cathepsin B== | ||
<StructureSection load='3cbk' size='340' side='right'caption='[[3cbk]], [[Resolution|resolution]] 2.67Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3cbk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Trypanosoma_cruzi Trypanosoma cruzi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CBK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CBK FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.67Å</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=3cbk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cbk OCA], [https://pdbe.org/3cbk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cbk RCSB], [https://www.ebi.ac.uk/pdbsum/3cbk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cbk ProSAT]</span></td></tr> | ||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CATB_HUMAN CATB_HUMAN] Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Has also been implicated in tumor invasion and metastasis. | |||
== 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/cb/3cbk_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=3cbk ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Cathepsin B is a papain-like cysteine protease showing both endo- and exopeptidase activity, the latter due to a unique occluding loop that restricts access to the active site cleft. To clarify the mode by which natural protein inhibitors manage to overcome this obstacle, we have analyzed the structure and function of cathepsin B in complexes with the Trypanosoma cruzi inhibitor, chagasin. Kinetic analysis revealed that substitution of His-110e, which anchors the loop in occluding position, results in 3-fold increased chagasin affinity (Ki for H110A cathepsin B, 0.35 nm) due to an improved association rate (kon, 5 x 10(5) m(-1)s(-1)). The structure of chagasin in complex with cathepsin B was solved in two crystal forms (1.8 and 2.67 angstroms resolution), demonstrating that the occluding loop is displaced to allow chagasin binding with its three loops, L4, L2, and L6, spanning the entire active site cleft. The occluding loop is differently displaced in the two structures, indicating a large range of movement and adoption of conformations forced by the inhibitor. The area of contact is slightly larger than in chagasin complexes with the endopeptidase, cathepsin L. However, residues important for high affinity to both enzymes are mainly found in the outer loops L4 and L6 of chagasin. The chagasin-cathepsin B complex provides a structural framework for modeling and design of inhibitors for cruzipain, the parasite cysteine protease and a virulence factor in Chagas disease. | |||
Displacement of the occluding loop by the parasite protein, chagasin, results in efficient inhibition of human cathepsin B.,Redzynia I, Ljunggren A, Abrahamson M, Mort JS, Krupa JC, Jaskolski M, Bujacz G J Biol Chem. 2008 Aug 15;283(33):22815-25. Epub 2008 May 30. PMID:18515357<ref>PMID:18515357</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3cbk" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Cathepsin 3D structures|Cathepsin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | |||
[[Category: Trypanosoma cruzi]] | [[Category: Trypanosoma cruzi]] | ||
[[Category: Abrahamson | [[Category: Abrahamson M]] | ||
[[Category: Bujacz | [[Category: Bujacz GD]] | ||
[[Category: Jaskolski | [[Category: Jaskolski M]] | ||
[[Category: Ljunggren | [[Category: Ljunggren A]] | ||
[[Category: Mort | [[Category: Mort JS]] | ||
[[Category: Redzynia | [[Category: Redzynia I]] | ||
Latest revision as of 12:44, 6 November 2024
chagasin-cathepsin Bchagasin-cathepsin B
Structural highlights
FunctionCATB_HUMAN Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Has also been implicated in tumor invasion and metastasis. 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 PubMedCathepsin B is a papain-like cysteine protease showing both endo- and exopeptidase activity, the latter due to a unique occluding loop that restricts access to the active site cleft. To clarify the mode by which natural protein inhibitors manage to overcome this obstacle, we have analyzed the structure and function of cathepsin B in complexes with the Trypanosoma cruzi inhibitor, chagasin. Kinetic analysis revealed that substitution of His-110e, which anchors the loop in occluding position, results in 3-fold increased chagasin affinity (Ki for H110A cathepsin B, 0.35 nm) due to an improved association rate (kon, 5 x 10(5) m(-1)s(-1)). The structure of chagasin in complex with cathepsin B was solved in two crystal forms (1.8 and 2.67 angstroms resolution), demonstrating that the occluding loop is displaced to allow chagasin binding with its three loops, L4, L2, and L6, spanning the entire active site cleft. The occluding loop is differently displaced in the two structures, indicating a large range of movement and adoption of conformations forced by the inhibitor. The area of contact is slightly larger than in chagasin complexes with the endopeptidase, cathepsin L. However, residues important for high affinity to both enzymes are mainly found in the outer loops L4 and L6 of chagasin. The chagasin-cathepsin B complex provides a structural framework for modeling and design of inhibitors for cruzipain, the parasite cysteine protease and a virulence factor in Chagas disease. Displacement of the occluding loop by the parasite protein, chagasin, results in efficient inhibition of human cathepsin B.,Redzynia I, Ljunggren A, Abrahamson M, Mort JS, Krupa JC, Jaskolski M, Bujacz G J Biol Chem. 2008 Aug 15;283(33):22815-25. Epub 2008 May 30. PMID:18515357[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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