Charge distribution in 7-methylguanine regarding cation-pi interaction with protein factor eIF4E.
Electric charge distribution in mRNA 5' cap terminus has been exhaustively characterized in respect to the affinity for cap-binding proteins. Formation of the stacked configuration of positively charged 7-methylguanine in between two aromatic amino acid rings, known as sandwich cation-pi stacking, is thought to be prerequisite for the specific recognition of the cap by eukaryotic initiation factor eIF4E; i.e., discrimination between the cap and nucleotides without the methyl group at N(7). Nuclear magnetic resonance spectroscopy of (15)N/(13)C-double-labeled 7-methylguanosine 5'-triphosphate and 7-methylguanosine, as well as their unsubstituted counterparts, GTP and guanosine, yielded characteristic changes of the electron-mediated spin-spin couplings and chemical shifts due to the methylation at N(7). The experimentally measured changes of the nuclear magnetic resonance parameters have been analyzed in respect to the electric charge distribution calculated by means of quantum chemical methods, and interpreted in terms of new proposed positive charge localization in the 7-methylguanine five-member ring.
Ruszczynska
Katarzyna
K
Department of Biophysics, Institute of Experimental Physics, Warsaw University, Warsaw, Poland.
Kamienska-Trela
Krystyna
K
Wojcik
Jacek
J
Stepinski
Janusz
J
Darzynkiewicz
Edward
E
Stolarski
Ryszard
R
D055592:Biophysical Phenomena; D001703:Biophysics; D002244:Carbon / Q000737:chemistry; D002412:Cations; D004583:Electrons; D039561:Eukaryotic Initiation Factor-4E / Q000737:chemistry*; D006147:Guanine / Q000031:analogs & derivatives / Q000737:chemistry*; D006151:Guanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D006160:Guanosine Triphosphate / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D008956:Models, Chemical; D012314:RNA Cap Analogs / Q000737:chemistry; D012315:RNA Caps; D012333:RNA, Messenger / Q000378:metabolism; D013696:Temperature
D002412:Cations; D039561:Eukaryotic Initiation Factor-4E; D012314:RNA Cap Analogs; D012315:RNA Caps; D012333:RNA, Messenger; D006151:Guanosine; C016578:7-methylguanosine; C017516:7-methylguanosine triphosphate; D006147:Guanine; C008450:7-methylguanine; D002244:Carbon; D006160:Guanosine Triphosphate