View source for 5vxa


==Structure of the human Mesh1-NADPH complex==
<StructureSection load='5vxa' size='340' side='right'caption='[[5vxa]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5vxa]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VXA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VXA FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HDDC3, MESH1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Guanosine-3',5'-bis(diphosphate)_3'-diphosphatase Guanosine-3',5'-bis(diphosphate) 3'-diphosphatase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.7.2 3.1.7.2] </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=5vxa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vxa OCA], [https://pdbe.org/5vxa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vxa RCSB], [https://www.ebi.ac.uk/pdbsum/5vxa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vxa ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/MESH1_HUMAN MESH1_HUMAN]] ppGpp hydrolyzing enzyme involved in starvation response.<ref>PMID:20818390</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Critical to the bacterial stringent response is the rapid relocation of resources from proliferation toward stress survival through the respective accumulation and degradation of (p)ppGpp by RelA and SpoT homologues. While mammalian genomes encode MESH1, a homologue of the bacterial (p)ppGpp hydrolase SpoT, neither (p)ppGpp nor its synthetase has been identified in mammalian cells. Here, we show that human MESH1 is an efficient cytosolic NADPH phosphatase that facilitates ferroptosis. Visualization of the MESH1-NADPH crystal structure revealed a bona fide affinity for the NADPH substrate. Ferroptosis-inducing erastin or cystine deprivation elevates MESH1, whose overexpression depletes NADPH and sensitizes cells to ferroptosis, whereas MESH1 depletion promotes ferroptosis survival by sustaining the levels of NADPH and GSH and by reducing lipid peroxidation. The ferroptotic protection by MESH1 depletion is ablated by suppression of the cytosolic NAD(H) kinase, NADK, but not its mitochondrial counterpart NADK2. Collectively, these data shed light on the importance of cytosolic NADPH levels and their regulation under ferroptosis-inducing conditions in mammalian cells.

MESH1 is a cytosolic NADPH phosphatase that regulates ferroptosis.,Ding CC, Rose J, Sun T, Wu J, Chen PH, Lin CC, Yang WH, Chen KY, Lee H, Xu E, Tian S, Akinwuntan J, Zhao J, Guan Z, Zhou P, Chi JT Nat Metab. 2020 Mar;2(3):270-277. doi: 10.1038/s42255-020-0181-1. Epub 2020 Mar, 9. PMID:32462112<ref>PMID:32462112</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5vxa" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Rose, J]]
[[Category: Zhou, P]]
[[Category: Hydrolase]]
[[Category: Mesh1 nadph]]