View source for 5iwh


==Structure of P. vulgaris HigB toxin delta H92==
<StructureSection load='5iwh' size='340' side='right'caption='[[5iwh]], [[Resolution|resolution]] 1.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5iwh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Proteus_vulgaris Proteus vulgaris]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IWH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IWH 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]] 1.101&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=5iwh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iwh OCA], [https://pdbe.org/5iwh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5iwh RCSB], [https://www.ebi.ac.uk/pdbsum/5iwh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5iwh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HIGB_PROVU HIGB_PROVU] Toxic component of a type II toxin-antitoxin (TA) module (PubMed:19423702, PubMed:24257752, PubMed:8645296). A ribosome-associated translation-dependent mRNA interferase. Inhibits translation by sequence-specific cleavage of mRNA. Prefers either in-frame or out-of-frame 5'-AAA-3' codons (lysine). Cleaves also the first three AAAs of stretches of four or more A sequences. 20% of codons containing AA are cleaved and occassionally cuts even at a single A (PubMed:19423702).<ref>PMID:19423702</ref> <ref>PMID:24257752</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Bacteria encode multiple type II toxin-antitoxin modules that cleave ribosome-bound mRNAs in response to stress. All ribosome-dependent toxin family members structurally characterized to date adopt similar microbial RNase architectures despite possessing low sequence identities. Therefore, determining which residues are catalytically important in this specialized RNase family has been a challenge in the field. Structural studies of RelE and YoeB toxins bound to the ribosome provided significant insights but biochemical experiments with RelE were required to clearly demonstrate which residues are critical for acid-base catalysis of mRNA cleavage. Here, we solved an X-ray crystal structure of the wild-type, ribosome-dependent toxin HigB bound to the ribosome revealing potential catalytic residues proximal to the mRNA substrate. Using cell-based and biochemical assays, we further determined that HigB residues His54, Asp90, Tyr91 and His92 are critical for activity in vivo, while HigB H54A and Y91A variants have the largest effect on mRNA cleavage in vitro Comparison of X-ray crystal structures of two catalytically inactive HigB variants with 70S-HigB bound structures reveal that HigB active site residues undergo conformational rearrangements likely required for recognition of its mRNA substrate. These data support the emerging concept that ribosome-dependent toxins have diverse modes of mRNA recognition.

Mechanism of endonuclease cleavage by the HigB toxin.,Schureck MA, Repack A, Miles SJ, Marquez J, Dunham CM Nucleic Acids Res. 2016 Jul 4. pii: gkw598. PMID:27378776<ref>PMID:27378776</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5iwh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Proteus vulgaris]]
[[Category: Dunham CM]]
[[Category: Marquez J]]
[[Category: Miles SJ]]
[[Category: Repack AA]]
[[Category: Schureck MA]]