The Role of Conserved Residues in the DEDDh Motif: the Proton-Transfer Mechanism of HIV-1 RNase H

  title={The Role of Conserved Residues in the DEDDh Motif: the Proton-Transfer Mechanism of HIV-1 RNase H},
  author={Simon L. D{\"u}rr and Olga Bohuszewicz and D{\'e}nes Berta and Reynier Suard{\'i}az and Pablo G. Jambrina and Christine Peter and Yihan Shao and Edina Rosta},
  journal={ACS Catalysis},
1 Citations
Catalytic Fields as a Tool to Analyze Enzyme Reaction Mechanism Variants and Reaction Steps
Catalytic fields representing the topology of the optimal molecular environment charge distribution that reduces the activation barrier have been used to examine alternative reaction variants and to


All-Atom Simulations Decrypt the Molecular Terms of RNA Catalysis in the Exon-Ligation Step of the Spliceosome
The spliceosome, a protein-directed metallo-ribozyme, catalyzes premature mRNA splicing via two transesterification reactions. The atomic-level details of the splicing mechanism and the role of the...
Catalytic Mechanism of Non-Target DNA Cleavage in CRISPR-Cas9 Revealed by Ab Initio Molecular Dynamics.
The non-target DNA cleavage catalysis described here resolves a fundamental open question in the CRISPR-Cas9 biology and provides valuable insights for improving the catalytic efficiency and the metal-dependent function of the Cas9 enzyme, which are at the basis of the development of genome editing tools.
How Does the Spliceosome Catalyze Intron Lariat Formation? Insights from Quantum Mechanics/Molecular Mechanics Free-Energy Simulations.
The proposed two-metal-ion mechanism provides a novel insight into understanding of the splicing reaction catalyzed by the spliceosome and is used to calculate the free-energy profile along the reaction pathway.
Structure and Dynamics of the CRISPR-Cas9 Catalytic Complex
  • G. Palermo
  • Biology, Chemistry
    J. Chem. Inf. Model.
  • 2019
An in-depth characterization of the active site chemistry of CRISPR-Cas9 is delivered by using quantum-classical molecular dynamics simulations and a Gaussian accelerated MD method, coupled with bioinformatics analysis, revealing a two-metal aided architecture in the RuvC active site, which is poised to operate DNA cleavages, in analogy with other DNA/RNA processing enzymes.
Cation trafficking propels RNA hydrolysis
Time-resolved X-ray crystal structures of RNA hydrolysis by RNase H1 reveal that cations in addition to the two canonical Mg2+ ions position the reactants in the active site and enable catalysis.
Exploring the Role of the Third Active Site Metal Ion in DNA Polymerase η with QM/MM Free Energy Simulations.
The simulations with three metal ions in the active site suggest that the third metal ion may play a catalytic role through electrostatic interactions with the leaving group, making the phosphoryl transfer reaction more thermodynamically favorable with a lower free energy barrier relative to the activated state corresponding to the deprotonated 3'OH nucleophile.
SWISS-MODEL: homology modelling of protein structures and complexes
An update to the SWISS-MODEL server is presented, which includes the implementation of a new modelling engine, ProMod3, and the introduction a new local model quality estimation method, QMEANDisCo.
Structure of HIV-1 reverse transcriptase cleaving RNA in an RNA/DNA hybrid
The 2.65-Å resolution structure of HIV-1 RT engaging in cleaving RNA in an RNA/DNA hybrid is reported and an inhibitor specific for the viral RNase H but not for its cellular homologs is identified.
CRISPR-Cas9 Structures and Mechanisms.
This review aims to provide an in-depth mechanistic and structural understanding of Cas9-mediated RNA-guided DNA targeting and cleavage and provides a framework for rational engineering aimed at altering catalytic function, guide RNA specificity, and PAM requirements and reducing off-target activity for the development of Cas 9-based therapies against genetic diseases.