2c34: Difference between revisions
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< | ==Leishmania mexicana ICP== | ||
<StructureSection load='2c34' size='340' side='right'caption='[[2c34]]' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2c34]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Leishmania_mexicana Leishmania mexicana]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C34 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2C34 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2c34 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c34 OCA], [https://pdbe.org/2c34 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2c34 RCSB], [https://www.ebi.ac.uk/pdbsum/2c34 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2c34 ProSAT]</span></td></tr> | ||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q868H1_LEIME Q868H1_LEIME] | |||
== 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/c3/2c34_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/main_output.php?pdb_ID=2c34 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Clan CA, family C1 cysteine peptidases (CPs) are important virulence factors and drug targets in parasites that cause neglected diseases. Natural CP inhibitors of the I42 family, known as ICP, occur in some protozoa and bacterial pathogens but are absent from metazoa. They are active against both parasite and mammalian CPs, despite having no sequence similarity with other classes of CP inhibitor. Recent data suggest that Leishmania mexicana ICP plays an important role in host-parasite interactions. We have now solved the structure of ICP from L. mexicana by NMR and shown that it adopts a type of immunoglobulin-like fold not previously reported in lower eukaryotes or bacteria. The structure places three loops containing highly conserved residues at one end of the molecule, one loop being highly mobile. Interaction studies with CPs confirm the importance of these loops for the interaction between ICP and CPs and suggest the mechanism of inhibition. Structure-guided mutagenesis of ICP has revealed that residues in the mobile loop are critical for CP inhibition. Data-driven docking models support the importance of the loops in the ICP-CP interaction. This study provides structural evidence for the convergent evolution from an immunoglobulin fold of CP inhibitors with a cystatin-like mechanism. | |||
The structure of Leishmania mexicana ICP provides evidence for convergent evolution of cysteine peptidase inhibitors.,Smith BO, Picken NC, Westrop GD, Bromek K, Mottram JC, Coombs GH J Biol Chem. 2006 Mar 3;281(9):5821-8. Epub 2005 Dec 28. PMID:16407198<ref>PMID:16407198</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2c34" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
== | |||
< | |||
[[Category: Leishmania mexicana]] | [[Category: Leishmania mexicana]] | ||
[[Category: Bromek | [[Category: Bromek K]] | ||
[[Category: Coombs | [[Category: Coombs GH]] | ||
[[Category: Mottram | [[Category: Mottram JC]] | ||
[[Category: Picken | [[Category: Picken NC]] | ||
[[Category: Smith | [[Category: Smith BO]] | ||
[[Category: Westrop | [[Category: Westrop GD]] | ||
Latest revision as of 08:34, 15 May 2024
Leishmania mexicana ICPLeishmania mexicana ICP
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedClan CA, family C1 cysteine peptidases (CPs) are important virulence factors and drug targets in parasites that cause neglected diseases. Natural CP inhibitors of the I42 family, known as ICP, occur in some protozoa and bacterial pathogens but are absent from metazoa. They are active against both parasite and mammalian CPs, despite having no sequence similarity with other classes of CP inhibitor. Recent data suggest that Leishmania mexicana ICP plays an important role in host-parasite interactions. We have now solved the structure of ICP from L. mexicana by NMR and shown that it adopts a type of immunoglobulin-like fold not previously reported in lower eukaryotes or bacteria. The structure places three loops containing highly conserved residues at one end of the molecule, one loop being highly mobile. Interaction studies with CPs confirm the importance of these loops for the interaction between ICP and CPs and suggest the mechanism of inhibition. Structure-guided mutagenesis of ICP has revealed that residues in the mobile loop are critical for CP inhibition. Data-driven docking models support the importance of the loops in the ICP-CP interaction. This study provides structural evidence for the convergent evolution from an immunoglobulin fold of CP inhibitors with a cystatin-like mechanism. The structure of Leishmania mexicana ICP provides evidence for convergent evolution of cysteine peptidase inhibitors.,Smith BO, Picken NC, Westrop GD, Bromek K, Mottram JC, Coombs GH J Biol Chem. 2006 Mar 3;281(9):5821-8. Epub 2005 Dec 28. PMID:16407198[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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