View source for 7ae8


==Crystal structure of HEPN(R102A) toxin==
<StructureSection load='7ae8' size='340' side='right'caption='[[7ae8]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ae8]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Aphanizomenon_flos-aquae_2012/KM1/D3 Aphanizomenon flos-aquae 2012/KM1/D3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AE8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AE8 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]] 2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</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=7ae8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ae8 OCA], [https://pdbe.org/7ae8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ae8 RCSB], [https://www.ebi.ac.uk/pdbsum/7ae8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ae8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HEPT_APHF2 HEPT_APHF2] Toxic component of a type VII toxin-antitoxin (TA) system. Upon cloning in E.coli inhibits cell growth for several hours; eventually cells recover and start growing. Cleaves the last 4 nucleotides from the tRNA acceptor stem (shown in vitro with E.coli tRNA-Glu(UUC)); only cleaves intact tRNA. Has no activity on mRNA. Neutralized by coexpression with cognate antitoxin MntA, which is due to di-AMPylation of the RNase.<ref>PMID:33290744</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Prokaryotic toxin-antitoxin (TA) systems are composed of a toxin capable of interfering with key cellular processes and its neutralizing antidote, the antitoxin. Here, we focus on the HEPN-MNT TA system encoded in the vicinity of a subtype I-D CRISPR-Cas system in the cyanobacterium Aphanizomenon flos-aquae. We show that HEPN acts as a toxic RNase, which cleaves off 4 nt from the 3' end in a subset of tRNAs, thereby interfering with translation. Surprisingly, we find that the MNT (minimal nucleotidyltransferase) antitoxin inhibits HEPN RNase through covalent di-AMPylation (diadenylylation) of a conserved tyrosine residue, Y109, in the active site loop. Furthermore, we present crystallographic snapshots of the di-AMPylation reaction at different stages that explain the mechanism of HEPN RNase inactivation. Finally, we propose that the HEPN-MNT system functions as a cellular ATP sensor that monitors ATP homeostasis and, at low ATP levels, releases active HEPN toxin.

HEPN-MNT Toxin-Antitoxin System: The HEPN Ribonuclease Is Neutralized by OligoAMPylation.,Songailiene I, Juozapaitis J, Tamulaitiene G, Ruksenaite A, Sulcius S, Sasnauskas G, Venclovas C, Siksnys V Mol Cell. 2020 Dec 17;80(6):955-970.e7. doi: 10.1016/j.molcel.2020.11.034. Epub, 2020 Dec 7. PMID:33290744<ref>PMID:33290744</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ae8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Aphanizomenon flos-aquae 2012/KM1/D3]]
[[Category: Large Structures]]
[[Category: Juozapaitis J]]
[[Category: Sasnauskas G]]
[[Category: Siksnys V]]
[[Category: Songailiene I]]
[[Category: Tamulaitiene G]]