6vcq

Crystal structure of E.coli RppH in complex with GTP

spinqualitylabelsall models 6vcq, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6vcq is a 1 chain structure with sequence from Ecoli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GTP, SO4 Related: 6vcn, 6vco, 6vcp, 6vck, 6vcl, 6vcm Gene: rppH, nudH, ygdP, b2830, JW2798 (ECOLI) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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