View source for 9ojq


==Crystal structure of E. coli ApaH in complex with ADP, active state==
<StructureSection load='9ojq' size='340' side='right'caption='[[9ojq]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9ojq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9OJQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9OJQ 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=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=9ojq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ojq OCA], [https://pdbe.org/9ojq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ojq RCSB], [https://www.ebi.ac.uk/pdbsum/9ojq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ojq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/APAH_ECOLI APAH_ECOLI] Hydrolyzes diadenosine 5',5'''-P1,P4-tetraphosphate to yield ADP.<ref>PMID:6317672</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Enigmatic dinucleoside tetraphosphates, known as 'alarmones' (Np(4)Ns), have recently been shown to function in bacteria as precursors to Np(4) caps on transcripts, likely influencing RNA longevity and cellular adaptation to stress. In proteobacteria, ApaH is the predominant enzyme that hydrolyzes Np(4)Ns and decaps Np(4)-capped RNAs to initiate their 5'-end-dependent degradation. Here we conducted a biochemical and structural study to uncover the catalytic mechanism of Escherichia coli ApaH, a prototypic symmetric Np(4)N hydrolase, on various Np(4)Ns and Np(4)-capped RNAs. We found that the enzyme uses a unique combination of nonspecific and semispecific substrate recognition, enabling substrates to bind in two orientations with a slight orientational preference. Despite such exceptional recognition properties, ApaH efficiently decaps various Np(4)-capped mRNAs and sRNAs, thereby impacting their lifetimes. Our findings highlight the need to determine substrate orientation preferences before designing substrate-mimicking drugs, as enzymes may escape activity modulation with one of the alternative substrate orientations.

ApaH decaps Np(4)N-capped RNAs in two alternative orientations.,Nuthanakanti A, Korn M, Levenson-Palmer R, Wu Y, Babu NR, Huang X, Banh RS, Belasco JG, Serganov A Nat Chem Biol. 2025 Aug 11. doi: 10.1038/s41589-025-01991-4. PMID:40789943<ref>PMID:40789943</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9ojq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Nuthanakanti A]]
[[Category: Serganov A]]