Evidence for a hydroxide ion bridging two magnesium ions at the active site of the hammerhead ribozyme - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Nucleic Acids Research Année : 1997

Evidence for a hydroxide ion bridging two magnesium ions at the active site of the hammerhead ribozyme

Pascal Auffinger
Eric Westhof
  • Fonction : Auteur
  • PersonId : 837072

Résumé

In the presence of magnesium ions, cleavage by the hammerhead ribozyme RNA at a specific residue leads to 2'3'-cyclic phosphate and 5'-OH extremities. In the cleavage reaction an activated ribose 2'-hydroxyl group attacks its attached 3'-phosphate. Molecular dynamics simulations of the crystal structure of the hammerhead ribozyme, obtained after flash-freezing of crystals under conditions where the ribozyme is active, provide evidence that a mu-bridging OH– ion is located between two Mg2+ ions close to the cleavable phosphate. Constrained simulations show further that a flip from the C3'-endo to the C2'-endo conformation of the ribose at the cleavable phosphate brings the 2'-hydroxyl in proximity to both the attacked phosphorous atom and the m-bridging OH– ion. Thus, the simulations lead to a detailed new insight into the mechanism of hammerhead ribozyme cleavage where a mu-hydroxo bridged magnesium cluster, located on the deep groove side, provides an OH– ion that is able to activate the 2'-hydroxyl nucleophile after a minor and localized conformational change in the RNA.
Fichier principal
Vignette du fichier
97_THermann_NAR_2033.pdf (1.04 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-03420489 , version 1 (11-10-2022)

Identifiants

Citer

Pascal Auffinger, Thomas Hermann, Scott G. Williams, Eric Westhof. Evidence for a hydroxide ion bridging two magnesium ions at the active site of the hammerhead ribozyme. Nucleic Acids Research, 1997, 25 (17), pp.3421-3427. ⟨10.1093/nar/25.17.3421⟩. ⟨hal-03420489⟩

Collections

CNRS SITE-ALSACE
16 Consultations
7 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More