Evidence for a Trajectory of Hydrolytic Reactions brought about by [L3Zn−OH] Species

Rombach, Michael; Maurer, Carsten; Weis, K. H.; Keller, Egbert; Vahrenkamp, Heinrich

doi:10.1002/(sici)1521-3765(19990301)5:3<1013::aid-chem1013>3.0.co;2-3

Cited by 49 publications

(8 citation statements)

References 38 publications

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“…[337][338][339][340][341][342] These tripodal ligands bind Zn II in a tetrahedral geometry and reduce the pK a of the fourth aqua ligand to ~6.5. 343 More importantly, the hydrophobic pocket, created by the pyrazole rings and the substituents at the 3-position, prevents the zinc ion from bridging two molecules of the ligand or a proton from bridging two zinc-containing complexes.…”

Section: Physical-organic Models Of the Active Site Of Camentioning

confidence: 91%

Carbonic Anhydrase as a Model for Biophysical and Physical-Organic Studies of Proteins and Protein−Ligand Binding

et al. 2008

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I. Introduction to Carbonic Anhydrase (CA) and to the Review 948 1. Introduction: Overview of CA as a Model 948 1.1. Value of Models 950 1.2. Objectives and Scope of the Review 950 2. Overview of Enzymatic Activity 950 3. Medical Relevance 951 II. Structure and Structure−Function Relationships of CA 953 4. Global and Active-Site Structure 953 4.1. Structure of Isoforms 953 4.2. Isolation and Purification 954 4.3. Crystallization 954 4.4. Structures Determined by X-ray Crystallography and NMR 955 4.4.1. Structures Determined by X-ray Crystallography 955 4.4.2. Structure Determined by NMR 955 4.5. Global Structural Features 963 4.6. Structure of the Binding Cavity 964 4.7. Zn II -Bound Water 965 5. Metalloenzyme Variants 966 6. Structure−Function Relationships in the Catalytic Active Site of CA 968 6.1. Effects of Ligands Directly Bound to Zn II 968 6.2. Effects of Indirect Ligands 969 7. Physical-Organic Models of the Active Site of CA 969 III. Using CA as a Model to Study Protein−Ligand Binding 970 8. Assays for Measuring Thermodynamic and Kinetic Parameters for Binding of Substrates and Inhibitors 970 8.1. Overview 970 8.

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Section: Physical-organic Models Of the Active Site Of Camentioning

confidence: 91%

Carbonic Anhydrase as a Model for Biophysical and Physical-Organic Studies of Proteins and Protein−Ligand Binding

et al. 2008

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“…Certain Zn(II) catalysts bind simple anionic ligands with a concomitant increase in coordination number while other Zn(II) complexes do not. [34][35][36] Such differences in binding interactions will depend on the flexibility of the multidentate or macrocyclic ligands in accommodating different Zn(II) complex coordination numbers and geometries.…”

Section: Binding Affinity Of Monoanions and Dianionsmentioning

confidence: 99%

A minimalist approach to understanding the efficiency of mononuclear Zn(ii) complexes as catalysts of cleavage of an RNA analog

et al. 2007

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Mononuclear complexes between Zn(2+) and the following four macrocycles were prepared: 1,4,7,10-tetraazacyclododecane (1), 1-oxa-4,7,10-triazacyclododecane (2), 1,5,9-triazacyclododecane (3) and 1-hydroxyethyl-1,4,7-triazacyclononane (4). The pH rate profiles of values of the observed second-order rate constant log (k(Zn))(app) for Zn(X)(OH(2))-catalyzed cleavage (X = 1, 2, 3 and 4) of 2-hydroxypropyl-4-nitrophenyl phosphate (HpPNP) show downward breaks centered at the pK(a) for ionization of the respective zinc bound water. At low pH, where the rate acceleration for the catalyzed reaction is largest, the stabilizing interaction between the catalyst and the bound transition state is 5.7, 7.4, 7.4 and 5.9 kcal mol(-1) for the reactions catalyzed by Zn(1)(OH(2)), Zn(2)(OH(2)), Zn(3)(OH(2)) and Zn(4)(OH(2)), respectively. The interactions between the metal cation and the macrocycle cause either a modest increase or reduction in transition state stabilization compared with 6.6 kcal mol(-1) stabilization for catalysis by Zn(OH(2))(6). The best Zn(II)-macrocycle catalysts are those for which the interactions between the metal ion and macrocycle are the weakest. Inhibition studies show that each of the four catalysts form complexes with phosphate and oxalate dianions with a much higher affinity than diethyl phosphate monoanion, consistent with stronger interaction of the catalysts with the transition state dianion compared with the substrate monoanion HpPNP. The pH-dependence of methyl phosphate inhibition of Zn(2) catalyzed cleavage of HpPNP shows that only the Zn(2)(OH(2)) species binds the inhibitor. This result is consistent with a mechanism that has Zn(2)(OH(2)) as the active catalytic species.

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“…Several computational studies have considered the details of this process, [2][3][4] and one of us has recently published structural evidence for the corresponding reaction trajectory. 5 While one would assume that in passing through the intermediate A, the Zn-O 1 bond is broken and the Zn-O 2 bond is formed, i.e. hydroxide is the leaving group, experimental proof for this reaction course is still missing.…”

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confidence: 99%

The TpZn–OH/CS2 reaction: theoretical and preparative visualization of an essential bioinorganic reaction path

et al. 2000

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Evidence for a Trajectory of Hydrolytic Reactions brought about by [L3Zn−OH] Species

Cited by 49 publications

References 38 publications

Carbonic Anhydrase as a Model for Biophysical and Physical-Organic Studies of Proteins and Protein−Ligand Binding

Carbonic Anhydrase as a Model for Biophysical and Physical-Organic Studies of Proteins and Protein−Ligand Binding

A minimalist approach to understanding the efficiency of mononuclear Zn(ii) complexes as catalysts of cleavage of an RNA analog

The TpZn–OH/CS2 reaction: theoretical and preparative visualization of an essential bioinorganic reaction path

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