9ojw | pdb_00009ojw

Crystal structure of E. coli ApaH in complex with ADP, inactive state

spinqualitylabelsall models 9ojw, resolution 1.96Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9ojw is a 2 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.96Å Ligands: ADP, EPE, GOL, MN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function APAH_ECOLI Hydrolyzes diadenosine 5',5-P1,P4-tetraphosphate to yield ADP. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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