View source for 6vcn


==Crystal structure of E.coli RppH in complex with ppcpG==
<StructureSection load='6vcn' size='340' side='right'caption='[[6vcn]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6vcn]] is a 1 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=6VCN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VCN 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]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G2P:PHOSPHOMETHYLPHOSPHONIC+ACID+GUANYLATE+ESTER'>G2P</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=6vcn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vcn OCA], [https://pdbe.org/6vcn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vcn RCSB], [https://www.ebi.ac.uk/pdbsum/6vcn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vcn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RPPH_ECOLI RPPH_ECOLI] Master regulator of 5'-dependent mRNA decay. Accelerates the degradation of transcripts by removing pyrophosphate from the 5'-end of triphosphorylated RNA, leading to a more labile monophosphorylated state that can stimulate subsequent ribonuclease cleavage. Preferentially hydrolyzes diadenosine penta-phosphate with ATP as one of the reaction products. Also able to hydrolyze diadenosine hexa- and tetra-phosphate. Has no activity on diadenosine tri-phosphate, ADP-ribose, NADH and UDP-glucose. In the meningitis causing strain E.coli K1, has been shown to play a role in HBMEC (human brain microvascular endothelial cells) invasion in vitro.<ref>PMID:10760174</ref> <ref>PMID:18202662</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
All enzymes face a challenge of discriminating cognate substrates from similar cellular compounds. Finding a correct substrate is especially difficult for the Escherichia coli Nudix hydrolase RppH, which triggers 5'-end-dependent RNA degradation by removing orthophosphate from the 5'-diphosphorylated transcripts. Here we show that RppH binds and slowly hydrolyzes NTPs, NDPs and (p)ppGpp, which each resemble the 5'-end of RNA. A series of X-ray crystal structures of RppH-nucleotide complexes, trapped in conformations either compatible or incompatible with hydrolysis, explain the low reaction rates of mononucleotides and suggest two distinct mechanisms for their hydrolysis. While RppH adopts the same catalytic arrangement with 5'-diphosphorylated nucleotides as with RNA, the enzyme hydrolyzes 5'-triphosphorylated nucleotides by extending the active site with an additional Mg2+ cation, which coordinates another reactive nucleophile. Although the average intracellular pH minimizes the hydrolysis of nucleotides by slowing their reaction with RppH, they nevertheless compete with RNA for binding and differentially inhibit the reactivity of RppH with triphosphorylated and diphosphorylated RNAs. Thus, E. coli RppH integrates various signals, such as competing non-cognate substrates and a stimulatory protein factor DapF, to achieve the differential degradation of transcripts involved in cellular processes important for the adaptation of bacteria to different growth conditions.

Principles of RNA and nucleotide discrimination by the RNA processing enzyme RppH.,Gao A, Vasilyev N, Kaushik A, Duan W, Serganov A Nucleic Acids Res. 2020 Jan 21. pii: 5710779. doi: 10.1093/nar/gkaa024. PMID:31960065<ref>PMID:31960065</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6vcn" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Duan W]]
[[Category: Gao A]]
[[Category: Kaushik A]]
[[Category: Serganov A]]
[[Category: Vasilyev N]]