View source for 5muf


==Crystal structure of human phosphoglycerate mutase family member 5 (PGAM5) in its enzymatically active dodecameric form induced by the presence of the N-terminal WDPNWD motif==
<StructureSection load='5muf' size='340' side='right'caption='[[5muf]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5muf]] is a 3 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=5MUF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MUF 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]] 3.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=5muf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5muf OCA], [https://pdbe.org/5muf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5muf RCSB], [https://www.ebi.ac.uk/pdbsum/5muf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5muf ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PGAM5_HUMAN PGAM5_HUMAN] Displays phosphatase activity for serine/threonine residues, and, dephosphorylates and activates MAP3K5 kinase. Has apparently no phosphoglycerate mutase activity. May be regulator of mitochondrial dynamics. Substrate for a KEAP1-dependent ubiquitin ligase complex. Contributes to the repression of NFE2L2-dependent gene expression. Acts as a central mediator for programmed necrosis induced by TNF, by reactive oxygen species and by calcium ionophore.<ref>PMID:18387606</ref> <ref>PMID:19590015</ref> <ref>PMID:22265414</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
PGAM5 is a mitochondrial membrane protein that functions as an atypical Ser/Thr phosphatase and is a regulator of oxidative stress response, necroptosis, and autophagy. Here we present several crystal structures of PGAM5 including the activating N-terminal regulatory sequences, providing a model for structural plasticity, dimerization of the catalytic domain, and the assembly into an enzymatically active dodecameric form. Oligomeric states observed in structures were supported by hydrogen exchange mass spectrometry, size-exclusion chromatography, and analytical ultracentrifugation experiments in solution. We report that the catalytically important N-terminal WDPNWD motif acts as a structural integrator assembling PGAM5 into a dodecamer, allosterically activating the phosphatase by promoting an ordering of the catalytic loop. Additionally the observed active site plasticity enabled visualization of essential conformational rearrangements of catalytic elements. The comprehensive biophysical characterization offers detailed structural models of this key mitochondrial phosphatase that has been associated with the development of diverse diseases.

Structures of PGAM5 Provide Insight into Active Site Plasticity and Multimeric Assembly.,Chaikuad A, Filippakopoulos P, Marcsisin SR, Picaud S, Schroder M, Sekine S, Ichijo H, Engen JR, Takeda K, Knapp S Structure. 2017 Jul 5;25(7):1089-1099.e3. doi: 10.1016/j.str.2017.05.020. Epub, 2017 Jun 22. PMID:28648608<ref>PMID:28648608</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5muf" style="background-color:#fffaf0;"></div>

==See Also==
*[[Protein phosphatase 3D structures|Protein phosphatase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Alfano I]]
[[Category: Arrowsmith CH]]
[[Category: Bountra C]]
[[Category: Chaikuad A]]
[[Category: Edwards AM]]
[[Category: Filippakopoulos P]]
[[Category: Knapp S]]
[[Category: Picaud S]]
[[Category: Von Delft F]]