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Review
. 2011 Sep 20;50(37):7835-41.
doi: 10.1021/bi201075b. Epub 2011 Aug 24.

Bovine Pancreatic Ribonuclease: Fifty Years of the First Enzymatic Reaction Mechanism

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Free PMC article
Review

Bovine Pancreatic Ribonuclease: Fifty Years of the First Enzymatic Reaction Mechanism

Claudi M Cuchillo et al. Biochemistry. .
Free PMC article

Abstract

Fifty years ago, the group of Tony Mathias and Bob Rabin at University College London deduced the first mechanism for catalysis by an enzyme, ribonuclease [Findlay, D., Herries, D. G., Mathias, A. P., Rabin, B. R., and Ross, C. A. (1961) Nature 190, 781-784]. Here, we celebrate this historic accomplishment by surveying knowledge of enzymology and protein science at that time, facts that led to the formulation of the mechanism, criticisms and alternative mechanisms, data that supported the proposed mechanism, and some of the refinements that have since provided a more precise picture of catalysis of RNA cleavage by ribonucleases. The Mathias and Rabin mechanism has appeared in numerous textbooks, monographs, and reviews and continues to have a profound impact on biochemistry.

Figures

Fig. 1
Fig. 1
Transphosphorylation and hydrolysis reactions catalyzed by RNase A. (Reproduced with permission from Scheme 1 of Cuchillo et al. (53).)
Fig. 2
Fig. 2
pH–Rate profiles for catalysis of the hydrolysis of cytidine 2′,3′-cyclic phosphate by RNase A. (A) Data. (B) Interpretative scheme. (C) Derived parameters. (Reproduced with permission from Fig. 6, Scheme 2, and Table 4 of Herries et al. (2).)
Fig. 3
Fig. 3
Solvent-dependence of the pH–rate profiles for catalysis of the hydrolysis of cytidine 2′,3′-cyclic phosphate by RNase A. (Reproduced with permission from Fig. 4 of Findlay et al. (4).)
Fig. 4
Fig. 4
Mechanism of Mathias and Rabin for catalysis of the hydrolysis (R = H) of cytidine 2′,3′-cyclic phosphate by RNase A. (Reproduced with permission from Fig. 2 of Findlay et al. (6).)
Fig. 5
Fig. 5
Model of the RNase A substrate complex. The substrate here is cytidine 2′,3′-cyclic cyclic phosphate. I and II are the imidazolyl groups of two histidine residues. III is an enzymic region that interacts with an alcohol or water. IV is the specificity region of the enzyme that interacts with the pyrimidine nucleobase of the substrate. (Reproduced with permission from Fig. 1 of Findlay et al. (6).)
Fig. 6
Fig. 6
Refined model of the RNase A substrate complex showing the interaction of an ammonium group with non-bridging oxygens of the phosphoryl group. (Reproduced with permission from Fig. 1 of Deavin et al. (36).)
Fig. 7
Fig. 7
Trigonal bipyramid formed during catalysis by RNase A. (Reproduced with permission from Fig. 12 of Rabin et al. (38 ).)
Fig. 8
Fig. 8
Subsites of RNase A. Bn, Rn, and pn are nucleobase-, ribose-, and phosphate-binding subsites, respectively, and are shown with their constituent residues. (Reproduced with permission from Fig. 1 of Moussaoui et al. (48).)
Fig. 9
Fig. 9
Hydrogen bonds formed by pyrimidine nucleobases and residues in the B1 subsite of RNase A. (Reproduced with permission from Fig. 3 of delCardayré and Raines (51).)

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