Structural Basis of Perturbed Pka Values of Catalytic Groups in Enzyme Active Sites

IUBMB

Life, 53: 85–98, 2002 Copyright c 2002 IUBMB 1521-6543/02 $12.00 + .00 DOI: 10.1080/10399710290038972

Review Article
Structural Basis of Perturbed pKa Values of Catalytic Groups in Enzyme Active Sites
Thomas K. Harris1 and George J. Turner2
Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Miami, Florida 2 Department of Physiology and Biophysics and the Neurosciences Program, University of Miami School of Medicine, Miami, Florida
1

Summary In protein and RNA macromolecules, only a limited number of different side-chain chemical groups are available to function as catalysts. The myriad of enzyme-catalyzed reactions results from the ability of most of these groups to function either as nucleophilic, electrophilic, or general acid–base catalysts, and the key to their adapted chemical function lies in their states of protonation. Ionization is determined by the intrinsic pKa of the group and the microenvironment created around the group by the protein or RNA structure, which perturbs its intrinsic pKa to its functional or apparent pKa . These pKa shifts result from interactions of the catalytic group with other fully or partially charged groups as well as the polarity or dielectric of the medium that surrounds it. The electroReceived 26 November 2001; accepted 28 January 2002. Address correspondence to Thomas K. Harris, University of Miami School of Medicine, Department of Biochemistry and Molecular Biology (R-629), P. O. Box 016129, Miami, FL 33101-6129, USA. Fax: [phone]. E-mail: [e-mail]

static interactions between ionizable groups found on the surface of macromolecules are weak and cause only slight pKa perturbations (2 units) and are the subject of this review. The magnitudes of these pKa perturbations are analyzed with respect to the structural details of the active-site microenvironment and the energetics of the reactions that they catalyze. IUBMB Life, 53: 85–98, 2002 Keywords

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