4af8: Difference between revisions

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==The structural basis for metacaspase substrate specificity and activation==
==The structural basis for metacaspase substrate specificity and activation==
<StructureSection load='4af8' size='340' side='right' caption='[[4af8]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
<StructureSection load='4af8' size='340' side='right'caption='[[4af8]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4af8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_(trypanozoon)_brucei Trypanosoma (trypanozoon) brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AF8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AF8 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4af8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei Trypanosoma brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AF8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AF8 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.4&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4afp|4afp]], [[4afr|4afr]], [[4afv|4afv]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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=4af8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4af8 OCA], [http://pdbe.org/4af8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4af8 RCSB], [http://www.ebi.ac.uk/pdbsum/4af8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4af8 ProSAT]</span></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=4af8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4af8 OCA], [https://pdbe.org/4af8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4af8 RCSB], [https://www.ebi.ac.uk/pdbsum/4af8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4af8 ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/MCA2_TRYB2 MCA2_TRYB2] Cysteine protease that cleaves specifically after arginine or lysine residues.<ref>PMID:18005666</ref> <ref>PMID:23506317</ref>  
Metacaspases are distantly related caspase-family cysteine peptidases implicated in programmed cell death in plants and lower eukaryotes. They differ significantly from caspases because they are calcium-activated, arginine-specific peptidases that do not require processing or dimerization for activity. To elucidate the basis of these differences and to determine the impact they might have on the control of cell death pathways in lower eukaryotes, the previously undescribed crystal structure of a metacaspase, an inactive mutant of metacaspase 2 (MCA2) from Trypanosoma brucei, has been determined to a resolution of 1.4 A. The structure comprises a core caspase fold, but with an unusual eight-stranded beta-sheet that stabilizes the protein as a monomer. Essential aspartic acid residues, in the predicted S1 binding pocket, delineate the arginine-specific substrate specificity. In addition, MCA2 possesses an unusual N terminus, which encircles the protein and traverses the catalytic dyad, with Y31 acting as a gatekeeper residue. The calcium-binding site is defined by samarium coordinated by four aspartic acid residues, whereas calcium binding itself induces an allosteric conformational change that could stabilize the active site in a fashion analogous to subunit processing in caspases. Collectively, these data give insights into the mechanistic basis of substrate specificity and mode of activation of MCA2 and provide a detailed framework for understanding the role of metacaspases in cell death pathways of lower eukaryotes.
 
Crystal structure of a Trypanosoma brucei metacaspase.,McLuskey K, Rudolf J, Proto WR, Isaacs NW, Coombs GH, Moss CX, Mottram JC Proc Natl Acad Sci U S A. 2012 May 8;109(19):7469-74. Epub 2012 Apr 23. PMID:22529389<ref>PMID:22529389</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4af8" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Caspase|Caspase]]
*[[Caspase 3D structures|Caspase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Coombs, G H]]
[[Category: Large Structures]]
[[Category: Isaacs, N W]]
[[Category: Trypanosoma brucei]]
[[Category: Mcluskey, K]]
[[Category: Coombs GH]]
[[Category: Moss, C X]]
[[Category: Isaacs NW]]
[[Category: Mottram, J C]]
[[Category: McLuskey K]]
[[Category: Rudolf, J]]
[[Category: Moss CX]]
[[Category: Caspase/hemoglobin fold]]
[[Category: Mottram JC]]
[[Category: Cysteine peptidase]]
[[Category: Rudolf J]]
[[Category: Hydrolase]]

Latest revision as of 10:14, 1 May 2024

The structural basis for metacaspase substrate specificity and activationThe structural basis for metacaspase substrate specificity and activation

Structural highlights

4af8 is a 1 chain structure with sequence from Trypanosoma brucei. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.4Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MCA2_TRYB2 Cysteine protease that cleaves specifically after arginine or lysine residues.[1] [2]

See Also

References

  1. ↑ Moss CX, Westrop GD, Juliano L, Coombs GH, Mottram JC. Metacaspase 2 of Trypanosoma brucei is a calcium-dependent cysteine peptidase active without processing. FEBS Lett. 2007 Dec 11;581(29):5635-9. PMID:18005666 doi:10.1016/j.febslet.2007.11.009
  2. ↑ Machado MF, Marcondes MF, Juliano MA, McLuskey K, Mottram JC, Moss CX, Juliano L, Oliveira V. Substrate specificity and the effect of calcium on Trypanosoma brucei metacaspase 2. FEBS J. 2013 Jun;280(11):2608-21. PMID:23506317 doi:10.1111/febs.12248

4af8, resolution 1.40Å

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