4s2w | pdb_00004s2w
Structure of E. coli RppH bound to sulfate ions
Structural highlights
Function[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.[1] [2] Publication Abstract from PubMed5'-end-dependent RNA degradation impacts virulence, stress responses, and DNA repair in bacteria by controlling the decay of hundreds of mRNAs. The RNA pyrophosphohydrolase RppH, a member of the Nudix hydrolase superfamily, triggers this degradation pathway by removing pyrophosphate from the triphosphorylated RNA 5' terminus. Here, we report the X-ray structures of Escherichia coli RppH (EcRppH) in apo and RNA-bound forms. These structures show distinct conformations of EcRppH-RNA complexes on the catalytic pathway and suggest a common catalytic mechanism for Nudix hydrolases. EcRppH interacts with RNA by a bipartite mechanism involving specific recognition of the 5'-terminal triphosphate and the second nucleotide, thus enabling discrimination against mononucleotides as substrates. The structures also reveal the molecular basis for the preference of the enzyme for RNA substrates bearing guanine in the second position by identifying a protein cleft in which guanine interacts with EcRppH side chains via cation-pi contacts and hydrogen bonds. These interactions explain the modest specificity of EcRppH at the 5' terminus and distinguish the enzyme from the highly selective RppH present in Bacillus subtilis. The divergent means by which RNA is recognized by these two functionally and structurally analogous enzymes has important implications for mRNA decay and the regulation of protein biosynthesis in bacteria. Structures of RNA Complexes with the Escherichia coli RNA Pyrophosphohydrolase RppH Unveil the Basis for Specific 5'-End-Dependent mRNA Decay*,Vasilyev N, Serganov A J Biol Chem. 2015 Feb 5. pii: jbc.M114.634824. PMID:25657011[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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