Temperature Effects on the Catalytic Efficiency, Rate Enhancement, and Transition State Affinity of Cytidine Deaminase, and the Thermodynamic Consequences for Catalysis of Removing a Substrate “Anchor”†

Biochemistry ◽  
2000 ◽  
Vol 39 (32) ◽  
pp. 9746-9753 ◽  
Author(s):  
Mark J. Snider ◽  
Stefan Gaunitz ◽  
Caroline Ridgway ◽  
Steven A. Short ◽  
Richard Wolfenden
Keyword(s):  
Transition State ◽  
Temperature Effects ◽  
Cytidine Deaminase ◽  
Catalytic Efficiency ◽  
Rate Enhancement ◽  
Efficiency Rate

ChemInform Abstract: SYNTHESIS OF 1,3-DIAZEPIN-2-ONE NUCLEOSIDES AS TRANSITION-STATE INHIBITORS OF CYTIDINE DEAMINASE

1980 ◽  
Vol 11 (48) ◽  
Author(s):  
V. E. MARQUEZ ◽  
P. S. LIU ◽  
J. A. KELLEY ◽  
J. S. DRISCOLL ◽  
J. J. MCCORMACK
Keyword(s):  
Transition State ◽  
Cytidine Deaminase

α-Retaining glucosyl transfer catalysed by trehalose phosphorylase from Schizophyllum commune: mechanistic evidence obtained from steady-state kinetic studies with substrate analogues and inhibitors

2001 ◽  
Vol 360 (3) ◽  
pp. 727-736 ◽  
Author(s):  
Bernd NIDETZKY ◽  
Christian EIS
Keyword(s):  
Steady State ◽  
Transition State ◽  
Schizophyllum Commune ◽  
Catalytic Efficiency ◽  
Kinetic Studies ◽  
Competitive Inhibitor ◽  
Chemical Mechanism ◽  
Steady State Kinetic ◽  
State Kinetic ◽  
Trehalose Phosphorylase

Fungal trehalose phosphorylase is classified as a family 4 glucosyltransferase that catalyses the reversible phosphorolysis of α,α-trehalose with net retention of anomeric configuration. Glucosyl transfer to and from phosphate takes place by the partly rate-limiting interconversion of ternary enzyme–substrate complexes formed from binary enzyme–phosphate and enzyme–α-d-glucopyranosyl phosphate adducts respectively. To advance a model of the chemical mechanism of trehalose phosphorylase, we performed a steady-state kinetic study with the purified enzyme from the basidiomycete fungus Schizophyllum commune by using alternative substrates, inhibitors and combinations thereof in pairs as specific probes of substrate-binding recognition and transition-state structure. Orthovanadate is a competitive inhibitor against phosphate and α-d-glucopyranosyl phosphate, and binds 3×104-fold tighter (Ki≈ 1μM) than phosphate. Structural alterations of d-glucose at C-2 and O-5 are tolerated by the enzyme at subsite +1. They lead to parallel effects of approximately the same magnitude (slope = 1.14; r2 = 0.98) on the reciprocal catalytic efficiency for reverse glucosyl transfer [log (Km/kcat)] and the apparent affinity of orthovanadate determined in the presence of the respective glucosyl acceptor (log Ki). An adduct of orthovanadate and the nucleophile/leaving group bound at subsite +1 is therefore the true inhibitor and displays partial transition state analogy. Isofagomine binds to subsite −1 in the enzyme–phosphate complex with a dissociation constant of 56μM and inhibits trehalose phosphorylase at least 20-fold better than 1-deoxynojirimycin. The specificity of the reversible azasugars inhibitors would be explained if a positive charge developed on C-1 rather than O-5 in the proposed glucosyl cation-like transition state of the reaction. The results are discussed in the context of α-retaining glucosyltransferase mechanisms that occur with and without a β-glucosyl enzyme intermediate.

Transition-state selectivity for a single hydroxyl group during catalysis by cytidine deaminase

Biochemistry ◽  
1995 ◽  
Vol 34 (14) ◽  
pp. 4516-4523 ◽  
Author(s):  
Shibin Xiang ◽  
Steven A. Short ◽  
Richard Wolfenden ◽  
Charles W. Carter
Keyword(s):  
Transition State ◽  
Cytidine Deaminase ◽  
Hydroxyl Group ◽  
State Selectivity

Synthesis of 1,3-diazepin-2-one nucleosides as transition-state inhibitors of cytidine deaminase

1980 ◽  
Vol 23 (7) ◽  
pp. 713-715 ◽  
Author(s):  
Victor E. Marquez ◽  
Paul S. Liu ◽  
James A. Kelley ◽  
John S. Driscoll ◽  
John J. McCormack
Keyword(s):  
Transition State ◽  
Cytidine Deaminase

Contributions of Conformational Compression and Preferential Transition State Stabilization to the Rate Enhancement by Chorismate Mutase

2003 ◽  
Vol 125 (23) ◽  
pp. 6892-6899 ◽  
Author(s):  
Cristiano Ruch Werneck Guimarães ◽  
Matthew P. Repasky ◽  
Jayaraman Chandrasekhar ◽  
Julian Tirado-Rives ◽  
William L. Jorgensen
Keyword(s):  
Transition State ◽  
Chorismate Mutase ◽  
Rate Enhancement ◽  
Transition State Stabilization

Cleavage of models for RNA mediated by a diZn(II) complex of bis[1,4-N1,N1′(1,5,9-triazacyclododecanyl)]butane in methanol and ethanol

2009 ◽  
Vol 87 (5) ◽  
pp. 640-649 ◽  
Author(s):  
C. Tony Liu ◽  
Stephanie A. Melnychuk ◽  
Chaomin Liu ◽  
Alexei A. Neverov ◽  
R. Stan Brown
Keyword(s):  
Transition State ◽  
Linear Dependence ◽  
Catalyst Concentration ◽  
Active Form ◽  
Catalytic Efficiency ◽  
Saturation Binding ◽  
Controlled Conditions ◽  
Versus Complex ◽  
Leaving Groups ◽  
Ph Controlled

The cleavage of seven RNA model 2-hydroxypropyl aryl phosphates (1) catalyzed by a dinuclear Zn(II) complex of bis[1,4-N1,N1′(1,5,9-triazacyclododecanyl)]butane (4) was studied in methanol and ethanol at 25 °C under pH controlled conditions. The results are compared with what was reported earlier for the dinuclear Zn(II) complex of the lower homologue bis[1,3-N1,N1′(1,5,9-triazacyclododecanyl)]propane (3). In methanol, the higher homologue exhibits saturation binding with substrates having poor aryloxy leaving groups. With good leaving groups there is an observed linear dependence of kobs versus complex concentration without saturation binding over the catalyst concentration range investigated. In ethanol, strong saturation binding between the active form of the catalyst ((RO–):Zn(II)2:4) and all substrates is observed, the results observed in both solvents being similar to what was reported for the lower (RO–):Zn(II)2:3 homologue. Energetics calculations are presented for the (RO–):Zn(II)2:4-catalyzed cleavage of each substrate in both solvents to assess the catalytic efficiency via the ΔΔG‡ for catalyst binding a transition state comprising [RO–:1]‡ or its kinetic equivalent.

scholarly journals Explaining Urease Specificity Towards Nickel: A Re-Analysis of Its Proposed Mechanism

2020 ◽  
Author(s):  
Millena Pereira Ferreira ◽  
Caio Bezerra de Castro ◽  
Caterina Gruenwaldt Cunha Marques Netto
Keyword(s):  
Catalytic Reaction ◽  
Catalytic Efficiency ◽  
Careful Analysis ◽  
Rate Enhancement ◽  
Nickel Centers

Urease is a binuclear metalloenzyme selective towards nickel, exhibiting a remarkable rate enhancement of the catalytic reaction. The accepted mechanism for urease describes the coordination of urea to both nickel centers in an O,N bridged mode, enabling the attack of the carbonyl by a bridged hydroxide present between the metallic centers. However, the substitution of nickel by other metals significantly reduces urease´s catalytic efficiency. The proposed mechanism cannot explain this difference in activity since it does not follow a rational nucleophilicity scale. After a careful analysis of the literature data on thermodynamics, kinetics, inhibition, and mutations, we verified that by analyzing the mechanism from a diffrent angle, another pathway is most likely occuring. This mechanism can explain urease´s selectivity towards nickel and all the data present in the literature, gathering amost a century of study about urease.

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