6p3q: Difference between revisions

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<StructureSection load='6p3q' size='340' side='right'caption='[[6p3q]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
<StructureSection load='6p3q' size='340' side='right'caption='[[6p3q]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6p3q]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P3Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6P3Q FirstGlance]. <br>
<table><tr><td colspan='2'>[[6p3q]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P3Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6P3Q FirstGlance]. <br>
</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=6p3q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p3q OCA], [http://pdbe.org/6p3q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6p3q RCSB], [http://www.ebi.ac.uk/pdbsum/6p3q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6p3q ProSAT]</span></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]] 2.8&#8491;</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=6p3q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p3q OCA], [https://pdbe.org/6p3q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6p3q RCSB], [https://www.ebi.ac.uk/pdbsum/6p3q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6p3q ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/CAN5_HUMAN CAN5_HUMAN]] Autosomal dominant neovascular inflammatory vitreoretinopathy. The disease is caused by mutations affecting the gene represented in this entry.  
[https://www.uniprot.org/uniprot/CAN5_HUMAN CAN5_HUMAN] Autosomal dominant neovascular inflammatory vitreoretinopathy. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/CAN5_HUMAN CAN5_HUMAN]] Calcium-regulated non-lysosomal thiol-protease.
[https://www.uniprot.org/uniprot/CAN5_HUMAN CAN5_HUMAN] Calcium-regulated non-lysosomal thiol-protease.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Increased calpain activity is linked to neuroinflammation including a heritable retinal disease caused by hyper-activating mutations in the calcium-activated calpain-5 (CAPN5) protease. Although structures for classical calpains are known, the structure of CAPN5, a non-classical calpain, remains undetermined. Here we report the 2.8 A crystal structure of the human CAPN5 protease core (CAPN5-PC). Compared to classical calpains, CAPN5-PC requires high calcium concentrations for maximal activity. Structure-based phylogenetic analysis and multiple sequence alignment reveal that CAPN5-PC contains three elongated flexible loops compared to its classical counterparts. The presence of a disease-causing mutation (c.799G&gt;A, p.Gly267Ser) on the unique PC2L2 loop reveals a function in this region for regulating enzymatic activity. This mechanism could be transferred to distant calpains, using synthetic calpain hybrids, suggesting an evolutionary mechanism for fine-tuning calpain function by modifying flexible loops. Further, the open (inactive) conformation of CAPN5-PC provides structural insight into CAPN5-specific residues that can guide inhibitor design.


Structural Insights into the Unique Activation Mechanisms of a Non-classical Calpain and Its Disease-Causing Variants.,Velez G, Sun YJ, Khan S, Yang J, Herrmann J, Chemudupati T, MacLaren RE, Gakhar L, Wakatsuki S, Bassuk AG, Mahajan VB Cell Rep. 2020 Jan 21;30(3):881-892.e5. doi: 10.1016/j.celrep.2019.12.077. PMID:31968260<ref>PMID:31968260</ref>
==See Also==
 
*[[Calpain 3D structures|Calpain 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6p3q" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Khan, S]]
[[Category: Khan S]]
[[Category: Koster, H J]]
[[Category: Koster HJ]]
[[Category: Lokesh, G]]
[[Category: Lokesh G]]
[[Category: Mahajan, V]]
[[Category: Mahajan V]]
[[Category: Sun, Y J]]
[[Category: Sun YJ]]
[[Category: Velez, G]]
[[Category: Velez G]]
[[Category: Yang, J]]
[[Category: Yang J]]
[[Category: Calcium binding protein]]
[[Category: Cystein protease]]
[[Category: Hydrolase]]
[[Category: Peptide binding protein]]
[[Category: Protease domain]]

Latest revision as of 14:53, 13 March 2024

Calpain-5 (CAPN5) Protease Core (PC)

6p3q, resolution 2.80Å

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