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Ionizable side chains at catalytic active sites of enzymes

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Abstract

Catalytic active sites of enzymes of known structure can be well defined by a modern program of computational geometry. The CASTp program was used to define and measure the volume of the catalytic active sites of 573 enzymes in the Catalytic Site Atlas database. The active sites are identified as catalytic because the amino acids they contain are known to participate in the chemical reaction catalyzed by the enzyme. Acid and base side chains are reliable markers of catalytic active sites. The catalytic active sites have 4 acid and 5 base side chains, in an average volume of 1,072 Å3. The number density of acid side chains is 8.3 M (in chemical units); the number density of basic side chains is 10.6 M. The catalytic active site of these enzymes is an unusual electrostatic and steric environment in which side chains and reactants are crowded together in a mixture more like an ionic liquid than an ideal infinitely dilute solution. The electrostatics and crowding of reactants and side chains seems likely to be important for catalytic function. In three types of analogous ion channels, simulation of crowded charges accounts for the main properties of selectivity measured in a wide range of solutions and concentrations. It seems wise to use mathematics designed to study interacting complex fluids when making models of the catalytic active sites of enzymes.

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Acknowledgments

Mr. Jimenez-Morales was supported by Becas Talentia Excellence Grant (Andalusian Ministry of Innovation, Science and Enterprise, Junta de Andalucia, Spain) and funding from Dr. Liang’s laboratory. Dr. Liang is supported by the NIH GM079804 and GM086145, and the NSF DBI 1062328 and DMS-0800257. Dr. Eisenberg was supported by NIH GM076013.

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  1. Department of Bioengineering, University of Illinois at Chicago, 851 S Morgan St., 218 SEO, Chicago, IL, 60607, USA

    David Jimenez-Morales, Jie Liang & Bob Eisenberg

  2. Department of Molecular Biophysics and Physiology, Rush University, 1653 West Congress Parkway, Chicago, IL, 60612, USA

    Bob Eisenberg

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Jimenez-Morales, D., Liang, J. & Eisenberg, B. Ionizable side chains at catalytic active sites of enzymes. Eur Biophys J 41, 449–460 (2012). https://doi.org/10.1007/s00249-012-0798-4

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