View source for 6yce


==Structure the bromelain protease from Ananas comosus with a thiomethylated active cysteine==
<StructureSection load='6yce' size='340' side='right'caption='[[6yce]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6yce]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Ananas_comosus Ananas comosus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YCE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YCE 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]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SCH:S-METHYL-THIO-CYSTEINE'>SCH</scene>, <scene name='pdbligand=XYS:XYLOPYRANOSE'>XYS</scene></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=6yce FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yce OCA], [https://pdbe.org/6yce PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yce RCSB], [https://www.ebi.ac.uk/pdbsum/6yce PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yce ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A199VSS3_ANACO A0A199VSS3_ANACO] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Ananas comosus stem extract is a complex mixture containing various cysteine proteases of the C1A subfamily, such as bromelain and ananain. This mixture used for centuries in Chinese medicine, has several potential therapeutic applications as anti-cancer, anti-inflammatory and ecchymosis degradation agent. In the present work we determined the structures of bromelain and ananain, both in their free forms and in complex with the inhibitors E64 and TLCK. These structures combined with protease-substrate complexes modeling clearly identified the Glu68 as responsible for the high discrimination of bromelain in favor of substrates with positively charged residues at P2, and unveil the reasons for its weak inhibition by cystatins and E64. Our results with purified and fully active bromelain, ananain and papain show a strong reduction of cell proliferation with MDA-MB231 and A2058 cancer cell lines at a concentration of about 1 muM, control experiments clearly emphasizing the need for proteolytic activity. In contrast, while bromelain and ananain had a strong effect on the proliferation of the OCI-LY19 and HL-60 non-adherent cell lines, papain, the archetypal member of the C1A subfamily, had none. This indicates that, in this case, sequence/structure identity beyond the active site of bromelain and ananain is more important than substrate specificity.

Structures of the free and inhibitors-bound forms of bromelain and ananain from Ananas comosus stem and in vitro study of their cytotoxicity.,Azarkan M, Maquoi E, Delbrassine F, Herman R, M'Rabet N, Calvo Esposito R, Charlier P, Kerff F Sci Rep. 2020 Nov 11;10(1):19570. doi: 10.1038/s41598-020-76172-5. PMID:33177555<ref>PMID:33177555</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6yce" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Ananas comosus]]
[[Category: Large Structures]]
[[Category: Azarkan M]]
[[Category: Calvo Esposito R]]
[[Category: Charlier P]]
[[Category: Delbrassine F]]
[[Category: Herman R]]
[[Category: Kerff F]]
[[Category: M Rabet N]]
[[Category: Sauvage E]]