Theoretical analyses on the role of metal cations in RNA cleavage processes.
Previously, we found that locations of metal cations in biomolecules, such as proteins and nucleotides, were in accord with predictions based on electrostatic-potential calculations of the nearest polar functional groups. Electrostatic potential of a cyclic oxyphosphorane dianion 2, which is a model compound for an intermediate or a transition state for the hammerhead ribozyme reaction, indicates that Mg2+ coordinations at the regions between axial (bridging) and equatorial (phosphoryl) oxygens are most favorable. If we consider the fact that negative charge is concentrated on two of the equatorial phosphoryl oxygens in the transition state 2, the axial-equatorial coordination is an unexpected result. Nevertheless, experimental results also support such an axial-equatorial coordination. Therefore, hammerhead ribozyme is a metalloenzyme in which at least one Mg2+ ion acts as a base and possibly a second Mg2+ ion acts as a Lewis acid. The double Mg2+ ion catalysis may be a common mechanism among various types of ribozyme and some protein enzymes as well.
Uchimaru
T
T
National Institute of Materials and Chemical Research, Agency of Industrial Science & Technology, MITI, Tsukuba Science City, Japan.
Tanabe
K
K
Shimayama
T
T
Uebayasi
M
M
Taira
K
K
D000818:Animals; D002412:Cations; D004563:Electrochemistry; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D008274:Magnesium / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry; D010753:Phosphoranes / Q000737:chemistry; D016337:RNA, Catalytic / Q000737:chemistry*; D016053:RNA, Protozoan / Q000737:chemistry*; D013768:Tetrahymena / Q000201:enzymology / Q000235:genetics
D002412:Cations; D009943:Organophosphorus Compounds; D010753:Phosphoranes; D016337:RNA, Catalytic; D016053:RNA, Protozoan; D008274:Magnesium