4g6s

Minimal Hairpin Ribozyme in the Transition State with A38P Variation

spinqualitylabelsall models 4g6s, resolution 2.84Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4g6s is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.84Å Ligands: 3DA, NCO, P5P, S9L, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed One mechanism by which ribozymes can accelerate biological reactions is by adopting folds that favorably perturb nucleobase ionization. Herein we used Raman crystallography to directly measure pK(a) values for the Ade38 N1 imino group of a hairpin ribozyme in distinct conformational states. A transition-state analogue gave a pK(a) value of 6.27 +/- 0.05, which agrees strikingly well with values measured by pH-rate analyses. To identify the chemical attributes that contribute to the shifted pK(a), we determined crystal structures of hairpin ribozyme variants containing single-atom substitutions at the active site and measured their respective Ade38 N1 pK(a) values. This approach led to the identification of a single interaction in the transition-state conformation that elevates the base pK(a) > 0.8 log unit relative to the precatalytic state. The agreement of the microscopic and macroscopic pK(a) values and the accompanying structural analysis supports a mechanism in which Ade38 N1(H)+ functions as a general acid in phosphodiester bond cleavage. Overall the results quantify the contribution of a single electrostatic interaction to base ionization, which has broad relevance for understanding how RNA structure can control chemical reactivity. A Transition-State Interaction Shifts Nucleobase Ionization toward Neutrality To Facilitate Small Ribozyme Catalysis.,Liberman JA, Guo M, Jenkins JL, Krucinska J, Chen Y, Carey PR, Wedekind JE J Am Chem Soc. 2012 Oct 17;134(41):16933-6. doi: 10.1021/ja3070528. Epub 2012 Oct, 3. PMID:22989273 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribozyme 3D structures

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