3m86: Difference between revisions

Latest revision as of 08:49, 6 September 2023

Crystal structure of the cysteine protease inhibitor, EhICP2, from Entamoeba histolytica

Structural highlights

3m86 is a 2 chain structure with sequence from Entamoeba histolytica HM-1:IMSS. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.65Å
Ligands:	1PE, CL, SO4
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

C4M2H5_ENTH1 Cysteine protease inhibitor (PubMed:16802137, PubMed:16979632, PubMed:21440496, PubMed:32731033, PubMed:20951777). Inhibits cysteine proteases CP1, CP2 and to a lesser extent CP5 (PubMed:16979632).^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Cysteine proteases (CP) are key pathogenesis and virulence determinants of protozoan parasites. Entamoeba histolytica contains at least 50 cysteine proteases; however, only three (EhCP1, EhCP2 and EhCP5) are responsible for approximately 90% of the cysteine protease activity in this parasite. CPs are expressed as inactive zymogens. Because the processed proteases are potentially cytotoxic, protozoan parasites have developed mechanisms to regulate their activity. Inhibitors of cysteine proteases (ICP) of the chagasin-like inhibitor family (MEROPS family I42) were recently identified in bacteria and protozoan parasites. E. histolytica contains two ICP-encoding genes of the chagasin-like inhibitor family. EhICP1 localizes to the cytosol, whereas EhICP2 is targeted to phagosomes. Herein, we report two crystal structures of EhICP2. The overall structure of EhICP2 consists of eight beta-strands and closely resembles the immunoglobulin fold. A comparison between the two crystal forms of EhICP2 indicates that the conserved BC, DE and FG loops form a flexible wedge that may block the active site of CPs. The positively charged surface of the wedge-forming loops in EhICP2 contrasts with the neutral surface of the wedge-forming loops in chagasin. We postulate that the flexibility and positive charge observed in the DE and FG loops of EhICP2 may be important to facilitate the initial binding of this inhibitor to the battery of CPs present in E. histolytica.

Crystal structure of the cysteine protease inhibitor 2 from Entamoeba histolytica: functional convergence of a common protein fold.,Casados-Vazquez LE, Lara-Gonzalez S, Brieba LG Gene. 2011 Jan 15;471(1-2):45-52. Epub 2010 Oct 15. PMID:20951777^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Sarić M, Vahrmann A, Bruchhaus I, Bakker-Grunwald T, Scholze H. The second cysteine protease inhibitor, EhICP2, has a different localization in trophozoites of Entamoeba histolytica than EhICP1. Parasitol Res. 2006 Dec;100(1):171-4. PMID:16802137 doi:10.1007/s00436-006-0206-z
↑ Sato D, Nakada-Tsukui K, Okada M, Nozaki T. Two cysteine protease inhibitors, EhICP1 and 2, localized in distinct compartments, negatively regulate secretion in Entamoeba histolytica. FEBS Lett. 2006 Oct 2;580(22):5306-12. PMID:16979632 doi:10.1016/j.febslet.2006.08.081
↑ Casados-Vazquez LE, Lara-Gonzalez S, Brieba LG. Crystal structure of the cysteine protease inhibitor 2 from Entamoeba histolytica: functional convergence of a common protein fold. Gene. 2011 Jan 15;471(1-2):45-52. Epub 2010 Oct 15. PMID:20951777 doi:10.1016/j.gene.2010.10.006
↑ Šarić M, Irmer H, Eckert D, Bär AK, Bruchhaus I, Scholze H. The cysteine protease inhibitors EhICP1 and EhICP2 perform different tasks in the regulation of endogenous protease activity in trophozoites of Entamoeba histolytica. Protist. 2012 Jan;163(1):116-28. PMID:21440496 doi:10.1016/j.protis.2011.01.003
↑ Flores-Solis D, Mendoza A, Rentería-González I, Casados-Vazquez LE, Trasviña-Arenas CH, Jiménez-Sandoval P, Benítez-Cardoza CG, Del Río-Portilla F, Brieba LG. Solution structure of the inhibitor of cysteine proteases 1 from Entamoeba histolytica reveals a possible auto regulatory mechanism. Biochim Biophys Acta Proteins Proteom. 2020 Nov;1868(11):140512. PMID:32731033 doi:10.1016/j.bbapap.2020.140512
↑ Casados-Vazquez LE, Lara-Gonzalez S, Brieba LG. Crystal structure of the cysteine protease inhibitor 2 from Entamoeba histolytica: functional convergence of a common protein fold. Gene. 2011 Jan 15;471(1-2):45-52. Epub 2010 Oct 15. PMID:20951777 doi:10.1016/j.gene.2010.10.006

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OCA

[1] Sarić M, Vahrmann A, Bruchhaus I, Bakker-Grunwald T, Scholze H. The second cysteine protease inhibitor, EhICP2, has a different localization in trophozoites of Entamoeba histolytica than EhICP1. Parasitol Res. 2006 Dec;100(1):171-4. PMID:16802137 doi:10.1007/s00436-006-0206-z

[2] Sato D, Nakada-Tsukui K, Okada M, Nozaki T. Two cysteine protease inhibitors, EhICP1 and 2, localized in distinct compartments, negatively regulate secretion in Entamoeba histolytica. FEBS Lett. 2006 Oct 2;580(22):5306-12. PMID:16979632 doi:10.1016/j.febslet.2006.08.081

[3] Casados-Vazquez LE, Lara-Gonzalez S, Brieba LG. Crystal structure of the cysteine protease inhibitor 2 from Entamoeba histolytica: functional convergence of a common protein fold. Gene. 2011 Jan 15;471(1-2):45-52. Epub 2010 Oct 15. PMID:20951777 doi:10.1016/j.gene.2010.10.006

[4] Šarić M, Irmer H, Eckert D, Bär AK, Bruchhaus I, Scholze H. The cysteine protease inhibitors EhICP1 and EhICP2 perform different tasks in the regulation of endogenous protease activity in trophozoites of Entamoeba histolytica. Protist. 2012 Jan;163(1):116-28. PMID:21440496 doi:10.1016/j.protis.2011.01.003

[5] Flores-Solis D, Mendoza A, Rentería-González I, Casados-Vazquez LE, Trasviña-Arenas CH, Jiménez-Sandoval P, Benítez-Cardoza CG, Del Río-Portilla F, Brieba LG. Solution structure of the inhibitor of cysteine proteases 1 from Entamoeba histolytica reveals a possible auto regulatory mechanism. Biochim Biophys Acta Proteins Proteom. 2020 Nov;1868(11):140512. PMID:32731033 doi:10.1016/j.bbapap.2020.140512

[6] Casados-Vazquez LE, Lara-Gonzalez S, Brieba LG. Crystal structure of the cysteine protease inhibitor 2 from Entamoeba histolytica: functional convergence of a common protein fold. Gene. 2011 Jan 15;471(1-2):45-52. Epub 2010 Oct 15. PMID:20951777 doi:10.1016/j.gene.2010.10.006

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@@ Line 3: / Line 3: @@
 <StructureSection load='3m86' size='340' side='right'caption='[[3m86]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3m86]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Entamoeba_histolytica_hm-1:imss Entamoeba histolytica hm-1:imss]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3M86 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3M86 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3m86]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Entamoeba_histolytica_HM-1:IMSS Entamoeba histolytica HM-1:IMSS]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3M86 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3M86 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.65&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3m88|3m88]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EHI_040460, ICP2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=294381 Entamoeba histolytica HM-1:IMSS])</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=3m86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3m86 OCA], [https://pdbe.org/3m86 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3m86 RCSB], [https://www.ebi.ac.uk/pdbsum/3m86 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3m86 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/C4M2H5_ENTH1 C4M2H5_ENTH1] Cysteine protease inhibitor (PubMed:16802137, PubMed:16979632, PubMed:21440496, PubMed:32731033, PubMed:20951777). Inhibits cysteine proteases CP1, CP2 and to a lesser extent CP5 (PubMed:16979632).<ref>PMID:16802137</ref> <ref>PMID:16979632</ref> <ref>PMID:20951777</ref> <ref>PMID:21440496</ref> <ref>PMID:32731033</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Entamoeba histolytica hm-1:imss]]
+[[Category: Entamoeba histolytica HM-1:IMSS]]
 [[Category: Large Structures]]
-[[Category: Brieba, L G]]
+[[Category: Brieba LG]]
-[[Category: Casados-Vazquez, L E]]
+[[Category: Casados-Vazquez LE]]
-[[Category: Lara-Gonzalez, S]]
+[[Category: Lara-Gonzalez S]]
-[[Category: Cysteine protease inhibitor]]
-[[Category: Protease]]
-[[Category: Protein binding]]

3m86: Difference between revisions

Latest revision as of 08:49, 6 September 2023

Crystal structure of the cysteine protease inhibitor, EhICP2, from Entamoeba histolytica

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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