View source for 8vj8


==X-ray Counterpart to Neutron Structure of Reduced Trp161Phe MnSOD==
<StructureSection load='8vj8' size='340' side='right'caption='[[8vj8]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8vj8]] 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=8VJ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8VJ8 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]] 1.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <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=8vj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8vj8 OCA], [https://pdbe.org/8vj8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8vj8 RCSB], [https://www.ebi.ac.uk/pdbsum/8vj8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8vj8 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/SODM_HUMAN SODM_HUMAN] Genetic variation in SOD2 is associated with susceptibility to microvascular complications of diabetes type 6 (MVCD6) [MIM:[https://omim.org/entry/612634 612634]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis.
== Function ==
[https://www.uniprot.org/uniprot/SODM_HUMAN SODM_HUMAN] Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.<ref>PMID:10334867</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human manganese superoxide dismutase (MnSOD) is a crucial oxidoreductase that maintains the vitality of mitochondria by converting O (2) (â-) to O (2) and H (2) O (2) with proton-coupled electron transfers (PCETs). Since changes in mitochondrial H (2) O (2) concentrations are capable of stimulating apoptotic signaling pathways, human MnSOD has evolutionarily gained the ability to be highly inhibited by its own product, H (2) O (2) . A separate set of PCETs is thought to regulate product inhibition, though mechanisms of PCETs are typically unknown due to difficulties in detecting the protonation states of specific residues that coincide with the electronic state of the redox center. To shed light on the underlying mechanism, we combined neutron diffraction and X-ray absorption spectroscopy of the product-bound, trivalent, and divalent states to reveal the all-atom structures and electronic configuration of the metal. The data identifies the product-inhibited complex for the first time and a PCET mechanism of inhibition is constructed.

Revealing the atomic and electronic mechanism of human manganese superoxide dismutase product inhibition.,Azadmanesh J, Slobodnik K, Struble LR, Lutz WE, Coates L, Weiss KL, Myles DAA, Kroll T, Borgstahl GEO bioRxiv [Preprint]. 2024 Jan 27:2024.01.26.577433. doi: , 10.1101/2024.01.26.577433. PMID:38328249<ref>PMID:38328249</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8vj8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Azadmanesh J]]
[[Category: Borgstahl GEO]]
[[Category: Kroll T]]
[[Category: Lutz WE]]
[[Category: Myles DAA]]
[[Category: Slobodnik K]]
[[Category: Struble LR]]
[[Category: Weiss KL]]