Solvent Protection of the Hammerhead Ribozyme in the Ground State:  Evidence for a Cation-Assisted Conformational Change Leading to Catalysis†

Biochemistry ◽  
2003 ◽  
Vol 42 (15) ◽  
pp. 4421-4429 ◽  
Author(s):  
Ken J. Hampel ◽  
John M. Burke
Keyword(s):  
Conformational Change ◽  
Ground State ◽  
Hammerhead Ribozyme

scholarly journals Biophysical and biochemical investigations of RNA catalysis in the hammerhead ribozyme

1999 ◽  
Vol 32 (3) ◽  
pp. 241-284 ◽  
Author(s):  
William G. Scott
Keyword(s):  
Metal Ions ◽  
Conformational Change ◽  
Large Scale ◽  
Enzyme Inhibitor ◽  
Hammerhead Ribozyme ◽  
Three Dimensional ◽  
Chemical Mechanism ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Hammerhead Rna

1. How do ribozymes work? 2412. The hammerhead RNA as a prototype ribozyme 2422.1 RNA enzymes 2422.2 Satellite self-cleaving RNAs 2422.3 Hammerhead RNAs and hammerhead ribozymes 2443. The chemical mechanism of hammerhead RNA self-cleavage 2463.1 Phosphodiester isomerization via an SN2(P) reaction 2473.2 The canonical role of divalent metal ions in the hammerhead ribozyme reaction 2513.3 The hammerhead ribozyme does not actually require metal ions for catalysis 2543.4 Hammerhead RNA enzyme kinetics 2574. Sequence requirements for hammerhead RNA self-cleavage 2604.1 The conserved core, mutagenesis and functional group modifications 2604.2 Ground-state vs. transition-state effects 2615. The three-dimensional structure of the hammerhead ribozyme 2625.1 Enzyme–inhibitor complexes 2625.2 Enzyme–substrate complex in the initial state 2645.3 Hammerhead ribozyme self-cleavage in the crystal 2645.4 The requirement for a conformational change 2655.5 Capture of conformational intermediates using crystallographic freeze-trapping 2665.6 The structure of a hammerhead ribozyme ‘early’ conformational intermediate 2675.7 The structure of a hammerhead ribozyme ‘later’ conformational intermediate 2685.8 Is the conformational change pH dependent? 2695.9 Isolating the structure of the cleavage product 2715.10 Evidence for and against additional large-scale conformation changes 2745.11 NMR spectroscopic studies of the hammerhead ribozyme 2786. Concluding remarks 2807. Acknowledgements 2818. References 2811. How do ribozymes work? 241The discovery that RNA can be an enzyme (Guerrier-Takada et al. 1983; Zaug & Cech, 1986) has created the fundamental question of how RNA enzymes work. Before this discovery, it was generally assumed that proteins were the only biopolymers that had sufficient complexity and chemical heterogeneity to catalyze biochemical reactions. Clearly, RNA can adopt sufficiently complex tertiary structures that make catalysis possible. How does the three- dimensional structure of an RNA endow it with catalytic activity? What structural and functional principles are unique to RNA enzymes (or ribozymes), and what principles are so fundamental that they are shared with protein enzymes?

A Conformational Change in the Catalytic Core of the Hammerhead Ribozyme upon Cleavage of an RNA Substrate†

Biochemistry ◽  
1997 ◽  
Vol 36 (3) ◽  
pp. 518-525 ◽  
Author(s):  
Jean-Pierre Simorre ◽  
Pascale Legault ◽  
Arlene B. Hangar ◽  
Paul Michiels ◽  
Arthur Pardi
Keyword(s):  
Conformational Change ◽  
Hammerhead Ribozyme ◽  
Catalytic Core

scholarly journals A fluorenylidene-acridane that becomes dark in color upon grinding – ground state mechanochromism by conformational change

2018 ◽  
Vol 9 (2) ◽  
pp. 475-482 ◽  
Author(s):  
Tsuyoshi Suzuki ◽  
Hiroshi Okada ◽  
Takafumi Nakagawa ◽  
Kazuki Komatsu ◽  
Chikako Fujimoto ◽  
...  
Keyword(s):  
Conformational Change ◽  
Ground State ◽  
Color Change

We report mechanochromic color change controlled by conformational change (folded and twisted conformers) of fluorenylidene-acridanes (FAs).

Modeling of a Possible Conformational Change Associated With the Catalytic Mechanism in the Hammerhead Ribozyme

1995 ◽  
Vol 13 (3) ◽  
pp. 515-522 ◽  
Author(s):  
Robert F. Setlik ◽  
Masayuki Shibata ◽  
Ramaswamy H. Sarma ◽  
Mukti H. Sarma ◽  
A. Latif Kazim ◽  
...  
Keyword(s):  
Conformational Change ◽  
Catalytic Mechanism ◽  
Hammerhead Ribozyme

scholarly journals Homologous ligands accommodated by discrete conformations of a buried cavity

2015 ◽  
Vol 112 (16) ◽  
pp. 5039-5044 ◽  
Author(s):  
Matthew Merski ◽  
Marcus Fischer ◽  
Trent E. Balius ◽  
Oliv Eidam ◽  
Brian K. Shoichet
Keyword(s):  
Conformational Change ◽  
Ground State ◽  
Main Chain ◽  
Ligand Design ◽  
Data Bank ◽  
T4 Lysozyme ◽  
Protein Conformations ◽  
Protein Conformational Change ◽  
Substantial Series ◽  
Alkyl Benzenes

Conformational change in protein–ligand complexes is widely modeled, but the protein accommodation expected on binding a congeneric series of ligands has received less attention. Given their use in medicinal chemistry, there are surprisingly few substantial series of congeneric ligand complexes in the Protein Data Bank (PDB). Here we determine the structures of eight alkyl benzenes, in single-methylene increases from benzene to n-hexylbenzene, bound to an enclosed cavity in T4 lysozyme. The volume of the apo cavity suffices to accommodate benzene but, even with toluene, larger cavity conformations become observable in the electron density, and over the series two other major conformations are observed. These involve discrete changes in main-chain conformation, expanding the site; few continuous changes in the site are observed. In most structures, two discrete protein conformations are observed simultaneously, and energetic considerations suggest that these conformations are low in energy relative to the ground state. An analysis of 121 lysozyme cavity structures in the PDB finds that these three conformations dominate the previously determined structures, largely modeled in a single conformation. An investigation of the few congeneric series in the PDB suggests that discrete changes are common adaptations to a series of growing ligands. The discrete, but relatively few, conformational states observed here, and their energetic accessibility, may have implications for anticipating protein conformational change in ligand design.

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