6uey

Pistol ribozyme transition-state analog vanadate

spinqualitylabelsall models 6uey, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6uey is a 4 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.8Å Ligands: MG, Q61 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Pistol ribozymes constitute a new class of small self-cleaving RNAs. We have solved crystal structures that provide three-dimensional snapshots along the reaction coordinate of pistol phosphodiester cleavage, corresponding to the pre-catalytic state, a vanadate mimic of the transition state, and the product. The resulting architectonic framework dictates the proposed underlying chemical mechanism, which is corroborated by functional assays that involve atomic mutagenesis of the ribozyme. Importantly, a hydrated Mg2+ ion remains innersphere-coordinated to N7-G33 in all three states. This is consistent with its likely role as acid in general acid base catalysis (delta and ss catalysis), supported further by the observation of a more than 1000-fold rate reduction if its positioning is impaired by deletion of the N7 site. Strikingly, the new structures shed light on a second hydrated Mg2+ ion that approaches the scissile phosphate from its binding site in the pre-cleavage state to reach out for water-mediated H-bonding in the cyclophosphate product. Because this second hydrated Mg2+ ion is also close to the 6-oxygen atom of G40 (general base, gamma catalysis), its potential impact on activation of G40 has been experimentally evaluated, however, the major role of the second Mg2+ ion appears to be the stabilization of product conformation. Together, our study delivers a mechanistic understanding of ribozyme-catalyzed backbone cleavage with unprecedented precision. On crucial roles of two hydrated Mg2+ ions in reaction catalysis of the pistol ribozyme.,Teplova M, Falschlunger C, Krasheninina O, Egger M, Ren A, Patel DJ, Micura R Angew Chem Int Ed Engl. 2019 Dec 5. doi: 10.1002/anie.201912522. PMID:31804735 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribozyme 3D structures

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