Kinetics of complex formation between human carbonic anhydrases and aromatic sulfonamides

Taylor, Palmer; King, Roy W.; Burgen, A. S. V.

doi:10.1021/bi00815a012

Cited by 124 publications

(80 citation statements)

References 12 publications

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“…Aliquots (one-third) from the same bead eluate were assayed against each isozyme. Concentrations of the two isozymes were matched using s1% values from the literature (21), and the [DNSA] was varied according to the literature values for Kd (DNSA) of the isozymes (22).…”

Section: Methodsmentioning

confidence: 99%

A paradigm for drug discovery employing encoded combinatorial libraries.

Burbaum¹,

Ohlmeyer²,

Reader³

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

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Section: Methodsmentioning

confidence: 99%

A paradigm for drug discovery employing encoded combinatorial libraries.

Burbaum¹,

Ohlmeyer²,

Reader³

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

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“…38,157,456,457 Other stopped-flow experiments, based on fluorescence quenching of tryptophan residues, have been used to measure the kinetics of binding of sulfonamides to CA directly (see section 11 for further discussion). 389,390,458 Any sulfonamide with spectral transitions overlapping the tryptophan emission band is an effective quencher of the native fluorescence of the protein.…”

Section: Fluorescence and Absorbance Spectroscopymentioning

confidence: 99%

“…458 Using van't Hoff analysis (eq 14), they concluded that binding was driven by enthalpy with only a small contribution of entropy (Table 13). Their van't Hoff plot showed slight curvature; this observation suggests that the change in heat capacity upon complexation was nonzero over this temperature range and brings into question the quantitative accuracy of their results (see section 10.2.2).…”

Section: Influence Of Structural Perturbations Of the Head And Ring Rmentioning

confidence: 99%

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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“…The other investigated sulfonamide, dansylamide, was selected because it is highly fluorescent when bound to the enzyme (Chen and Kernohan, 1967). This inhibitor has previously been shown to have the opposite isozyme selectivity (Taylor et al, 1970), but the 100-fold preference for HCA I observed by us at pH 8 is larger than reported by Taylor et al (1970). Consequently, the ratio K,(dansylamide)/K,(MK-417), denoted R in Table 5, is almost lo5 times larger for HCA I1 than for HCA I.…”

Section: Discussionmentioning

confidence: 54%

Catalytic and Inhibitor‐Binding Properties of Some Active‐Site Mutants of Human Carbonic Anhydrase I

Engstrand

Jonsson

Lindskog

1995

European Journal of Biochemistry

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Three isozyme-specific residues in the active site of human carbonic anhydrase I, Va162, His67, and His200, have been changed by site-directed mutagenesis to their counterparts in human carbonic anhydrase 11, Asn62, Asn67, and Thr200. A double mutant, containing Asn62 and Asn67, and a triple mutant, containing all three alterations, were also produced. The rates of CO, hydration and ester hydrolysis catalyzed by these mutants, the inhibition of these enzymes by the anions, SCN-, and I-, and the binding of the sulfonamide inhibitors, dansylamide and MK-417 (a thienothiopyran-2-sulfonamide) have been measured. The results suggest that the effect of His200 in isozyme I is to prolong the lifetime of the enzyme-bicarbonate complex and to increase the pK, of the catalytic group, a zinc-coordinated water molecule. For isozyme I, Val62 and His67 might interfere with the function of a proton 'shuttle' group in the active site, thus maintaining the buffer specificity of a compulsory proton-transfer step. The single mutations have small effects on anion binding. Only the triple mutant has anion-binding properties resembling those of isozyme 11. All mutants show altered sulfonamide-binding properties. In particular, the binding specificity is affected. While wild-type isozyme I binds dansylamide SO times more strongly than MK-417, the triple mutant shows a reversed selectivity and binds MK-417 nearly SO times more strongly than dansylamide.

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Kinetics of complex formation between human carbonic anhydrases and aromatic sulfonamides

Cited by 124 publications

References 12 publications

A paradigm for drug discovery employing encoded combinatorial libraries.

A paradigm for drug discovery employing encoded combinatorial libraries.

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

Catalytic and Inhibitor‐Binding Properties of Some Active‐Site Mutants of Human Carbonic Anhydrase I

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