The crystal structure of subtype-B HIV-1 genomic RNA Dimerization Initiation Site duplex revealed chain cleavage at a specific position resulting in 3'-phosphate and 5'-hydroxyl termini. A crystallographic analysis showed that Ba(2+), Mn(2+), Co(2+) and Zn(2+) bind specifically on a guanine base close to the cleaved position. The crystal structures also point to a necessary conformational change to induce an 'in-line' geometry at the cleavage site. In solution, divalent cations increased the rate of cleavage with pH/pKa compensation, indicating that a cation-bound hydroxide anion is responsible for the cleavage. We propose a 'Trojan horse' mechanism, possibly of general interest, wherein a doubly charged cation hosted near the cleavage site as a 'harmless' species is further transformed in situ into an 'aggressive' species carrying a hydroxide anion.
Cation-dependent cleavage of the duplex form of the subtype-B HIV-1 RNA dimerization initiation site.,Ennifar E, Walter P, Dumas P Nucleic Acids Res. 2010 Sep 1;38(17):5807-16. Epub 2010 May 11. PMID:20460458[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
↑ Ennifar E, Walter P, Dumas P. Cation-dependent cleavage of the duplex form of the subtype-B HIV-1 RNA dimerization initiation site. Nucleic Acids Res. 2010 Sep 1;38(17):5807-16. Epub 2010 May 11. PMID:20460458 doi:10.1093/nar/gkq344
