Crystallographic study of hydration of an internal cavity in engineered proteins with buried polar or ionizable groups

Biophysical Journal
Jamie L SchlessmanBertrand Garcia-Moreno E

Abstract

Although internal water molecules are essential for the structure and function of many proteins, the structural and physical factors that govern internal hydration are poorly understood. We have examined the molecular determinants of internal hydration systematically, by solving the crystal structures of variants of staphylococcal nuclease with Gln-66, Asn-66, and Tyr-66 at cryo (100 K) and room (298 K) temperatures, and comparing them with existing cryo and room temperature structures of variants with Glu-66, Asp-66, Lys-66, Glu-92 or Lys-92 obtained under conditions of pH where the internal ionizable groups are in the neutral state. At cryogenic temperatures the polar moieties of all these internal side chains are hydrated except in the cases of Lys-66 and Lys-92. At room temperature the internal water molecules were observed only in variants with Glu-66 and Tyr-66; water molecules in the other variants are probably present but they are disordered and therefore undetectable crystallographically. Each internal water molecule establishes between 3 and 5 hydrogen bonds with the protein or with other internal water molecules. The strength of interactions between internal polar side chains and water molecules seems to decrease fro...Continue Reading

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Citations

May 27, 2011·Journal of Chemical Information and Modeling·Yiyu LiIan S Haworth
Aug 28, 2010·Proceedings of the National Academy of Sciences of the United States of America·Daniel G IsomBertrand García-Moreno E
Mar 11, 2011·Proceedings of the National Academy of Sciences of the United States of America·Daniel G IsomBertrand García-Moreno
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Aug 8, 2014·Biophysical Journal·Raul Araya-SecchiRuhong Zhou
Nov 10, 2010·Journal of Molecular Biology·Michael S ChimentiBertrand García-Moreno E
Nov 18, 2010·Biophysical Journal·Martin A SchroerRoland Winter
Aug 29, 2019·Journal of Molecular Recognition : JMR·Manuela Maurer, Chris Oostenbrink
Oct 5, 2018·Journal of the Royal Society, Interface·Julien Roche, Catherine A Royer
Sep 25, 2020·Journal of Computer-aided Molecular Design·Teresa Danielle BergazinDavid L Mobley
Oct 7, 2008·Journal of Chemical Information and Modeling·Ana DamjanovićBernard R Brooks
Feb 22, 2018·The Journal of Physical Chemistry. B·Aaron C RobinsonBertrand García-Moreno E

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