3cbk: Difference between revisions

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-{{STRUCTURE_3cbk|  PDB=3cbk  |  SCENE=  }}
+==chagasin-cathepsin B==
-===chagasin-cathepsin B===
+<StructureSection load='3cbk' size='340' side='right' caption='[[3cbk]], [[Resolution|resolution]] 2.67&Aring;' scene=''>
-{{ABSTRACT_PUBMED_18515357}}
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3cbk]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Trycr Trycr]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CBK FirstGlance]. <br>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2nqd|2nqd]], [[2nnr|2nnr]], [[1huc|1huc]], [[3pbh|3pbh]], [[3cbj|3cbj]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CTSB, CPSB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), cha ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5693 TRYCR])</td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cathepsin_B Cathepsin B], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.1 3.4.22.1] </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=3cbk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cbk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3cbk RCSB], [http://www.ebi.ac.uk/pdbsum/3cbk PDBsum]</span></td></tr>
+</table>
+== 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/initialview01.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/chain_selection.php?pdb_ID=2ata 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.
-==Function==
+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>
-[[http://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.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[3cbk]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CBK OCA].
+</div>
 ==See Also==
 *[[Cathepsin|Cathepsin]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:018515357</ref><references group="xtra"/><references/>
+__TOC__
+</StructureSection>
 [[Category: Cathepsin B]]
+[[Category: Human]]
+[[Category: Trycr]]
 [[Category: Abrahamson, M.]]
 [[Category: Bujacz, G D.]]