View source for 7smg


==Crystal structure of a (p)ppApp hydrolase from Bacteroides caccae==
<StructureSection load='7smg' size='340' side='right'caption='[[7smg]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7smg]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacteroides_caccae_ATCC_43185 Bacteroides caccae ATCC 43185]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SMG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SMG 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]] 2.3&#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>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=7smg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7smg OCA], [https://pdbe.org/7smg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7smg RCSB], [https://www.ebi.ac.uk/pdbsum/7smg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7smg ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Bacteria produce a variety of nucleotide second messengers to adapt to their surroundings. Although chemically similar, the nucleotides guanosine penta- and tetraphosphate [(p)ppGpp] and adenosine penta- and tetraphosphate [(p)ppApp] have distinct functions in bacteria. (p)ppGpp mediates survival under nutrient-limiting conditions and its intracellular levels are regulated by synthetases and hydrolases belonging to the RelA-SpoT homolog (RSH) family of enzymes. By contrast, (p)ppApp is not known to be involved in nutrient stress responses and is synthesized by RSH-resembling toxins that inhibit the growth of bacterial cells. However, it remains unclear whether there exists a family of hydrolases that specifically act on (p)ppApp to reverse its toxic effects. Here, we present the structure and biochemical characterization of adenosine 3'-pyrophosphohydrolase 1 (Aph1), the founding member of a monofunctional (p)ppApp hydrolase family of enzymes. Our work reveals that Aph1 adopts a histidine-aspartate (HD)-domain fold characteristic of phosphohydrolase metalloenzymes and its activity mitigates the growth inhibitory effects of (p)ppApp-synthesizing toxins. Using an informatic approach, we identify over 2,000 putative (p)ppApp hydrolases that are widely distributed across bacterial phyla and found in diverse genomic contexts, and we demonstrate that 12 representative members hydrolyze ppApp. In addition, our in silico analyses reveal a unique molecular signature that is specific to (p)ppApp hydrolases, and we show that mutation of two residues within this signature broadens the specificity of Aph1 to promiscuously hydrolyze (p)ppGpp in vitro. Overall, our findings indicate that like (p)ppGpp hydrolases, (p)ppApp hydrolases are widespread in bacteria and may play important and underappreciated role(s) in bacterial physiology.

Identification of a broadly conserved family of enzymes that hydrolyze (p)ppApp.,Ahmad S, Gordon IJ, Tsang KK, Alexei AG, Sychantha D, Colautti J, Trilesky SL, Kim Y, Wang B, Whitney JC Proc Natl Acad Sci U S A. 2023 Apr 4;120(14):e2213771120. doi: , 10.1073/pnas.2213771120. Epub 2023 Mar 29. PMID:36989297<ref>PMID:36989297</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7smg" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bacteroides caccae ATCC 43185]]
[[Category: Large Structures]]
[[Category: Ahmad S]]
[[Category: Alexei AG]]
[[Category: Kim Y]]
[[Category: Trilesky S]]
[[Category: Tsang KK]]
[[Category: Whitney JC]]