Catalysis by entropic effects: the action of cytidine deaminase on 5,6-dihydrocytidine

Biochemistry
Mark J SniderR Wolfenden

Abstract

In neutral solution, 5,6-dihydrocytidine undergoes spontaneous deamination (k25 approximately 3.2 x 10(-5) s(-1)) much more rapidly than does cytidine (k25 approximately 3.0 x 10(-10) s(-1)), with a more favorable enthalpy of activation (DeltaDeltaH# = -8.7 kcal/mol) compensated by a less favorable entropy of activation (TDeltaDeltaS# = -1.8 kcal/mol at 25 degrees C). E. coli cytidine deaminase enhances the rate of deamination of 5,6-dihydrocytidine (kcat/k(non) = 4.4 x 10(5)) by enhancing the entropy of activation (DeltaDeltaH# = 0 kcal/mol; TDeltaDeltaS# = +7.6 kcal/mol, at 25 degrees C). Binding of the competitive inhibitor 3,4,5,6-tetrahydrouridine (THU), a stable analogue of 5,6-dihydrocytidine in the transition state for its deamination, is accompanied by a release of enthalpy (DeltaH = -7.1 kcal/mol, TDeltaDeltaS = +2.2 kcal/mol) that approaches the estimated enthalpy of binding of the actual substrate in the transition state for deamination of 5,6-dihydrocytidine (DeltaH = -8.1 kcal/mol, TDeltaDeltaS = +6.0 kcal/mol). Thus, the shortcomings of THU in capturing all of the binding affinity expected of an ideal transition-state analogue reflect a less favorable entropy of association. That difference may arise from the ana...Continue Reading

References

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Citations

Sep 23, 2003·Biophysical Chemistry·Richard Wolfenden
Feb 27, 2009·Chemical Reviews·Francisca E Reyes-Turcu, Keith D Wilkinson
Jan 22, 2008·Applied and Environmental Microbiology·Debora Frigi Rodrigues, James M Tiedje
Jun 8, 2006·Annual Review of Biochemistry·Khawar Sohail Siddiqui, Ricardo Cavicchioli
Sep 23, 2003·Journal of Pharmaceutical Sciences·Tian-Xiang XiangBradley D Anderson
Jun 2, 2015·Nature Communications·Masoud Kazemi, Johan Åqvist
Dec 2, 2004·Biochimica Et Biophysica Acta·Alexander Y Amerik, Mark Hochstrasser
Apr 16, 2005·The Journal of Biological Chemistry·Mack SobhanyMasahiko Negishi

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