Substrate specificity of an active dinuclear Zn(II) catalyst for cleavage of RNA analogues and a dinucleoside.
The cleavage of the diribonucleoside UpU (uridylyl-3'-5'-uridine) to form uridine and uridine (2',3')-cyclic phosphate catalyzed by the dinuclear Zn(II) complex of 1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropane (Zn(2)(1)(H(2)O)) has been studied at pH 7-10 and 25 degrees C. The kinetic data are consistent with the accumulation of a complex between catalyst and substrate and were analyzed to give values of k(c) (s(-)(1)), K(d) (M), and k(c)/K(d) (M(-)(1) s(-)(1)) for the Zn(2)(1)(H(2)O)-catalyzed reaction. The pH rate profile of values for log k(c)/K(d) for Zn(2)(1)(H(2)O)-catalyzed cleavage of UpU shows the same downward break centered at pH 7.8 as was observed in studies of catalysis of cleavage of 2-hydroxypropyl-4-nitrophenyl phosphate (HpPNP) and uridine-3'-4-nitrophenyl phosphate (UpPNP). At low pH, where the rate acceleration for the catalyzed reaction is largest, the stabilizing interaction between Zn(2)(1)(H(2)O) and the bound transition states is 9.3, 7.2, and 9.6 kcal/mol for the catalyzed reactions of UpU, UpPNP, and HpPNP, respectively. The larger transition-state stabilization for Zn(2)(1)(H(2)O)-catalyzed cleavage of UpU (9.3 kcal/mol) compared with UpPNP (7.2 kcal/mol) provides evidence that the transition state for the former reaction is stabilized by interactions between the catalyst and the C-5'-oxyanion of the basic alkoxy leaving group.
O'Donoghue
AnnMarie
A
Departments of Chemistry, University at Buffalo, State University of New York, Buffalo, New York 14260-3000, USA.
Pyun
Sang Yong
SY
Yang
Meng-Yin
MY
Morrow
Janet R
JR
Richard
John P
JP
D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry; D002384:Catalysis; D015226:Dinucleoside Phosphates / Q000737:chemistry*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009942:Organometallic Compounds / Q000737:chemistry; D010755:Organophosphates; D009943:Organophosphorus Compounds / Q000737:chemistry; D013379:Substrate Specificity; D014542:Uridine Monophosphate / Q000737:chemistry; D015032:Zinc / Q000737:chemistry*
C491495:1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropane; C436487:2-(hydroxypropyl)-4-nitrophenyl phosphate; D015226:Dinucleoside Phosphates; D006573:Heterocyclic Compounds, 1-Ring; D009942:Organometallic Compounds; D010755:Organophosphates; D009943:Organophosphorus Compounds; C026519:uridine monophosphate-uridine; D014542:Uridine Monophosphate; D015032:Zinc; D000409:Alanine