Conformational Reorganization Coupled to the Ionization of Internal Lys Residues in Proteins

Biochemistry
Daniel E RichmanBertrand García-Moreno E

Abstract

Ionizable groups buried in the hydrophobic interior of proteins are essential for energy transduction and catalysis. Because the protein interior is usually neither as polar nor as polarizable as water, these groups tend to have anomalous pKa values, and their ionization tends to be coupled to conformational reorganization. To elucidate mechanisms of energy transduction in proteins, it is necessary to understand the structural determinants of the pKa values of these buried groups, including the range and character of the conformational reorganization that the ionization of these buried groups can elicit. The L25K and L125K variants of staphylococcal nuclease (SNase) were used to characterize the diverse types of structural reorganization that can be promoted by the ionization of buried groups. NMR relaxation dispersion and ZZ-exchange experiments were used to identify the locations and measure the time scales and extent of pH-dependent conformational exchange in these two proteins. The buried Lys-25 and Lys-125 residues titrate with pKa of 6.3 and 6.2, respectively. The L25K protein fluctuates between the native state and an ensemble of locally unfolded states on the 400 μs to 7 ms time scale. On the 100 to 500 ms time scale th...Continue Reading

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Citations

Dec 24, 2016·Biochemistry·Aaron C RobinsonBertrand García-Moreno E
Aug 24, 2018·The Journal of Chemical Physics·Ana DamjanovicBernard R Brooks
Jul 3, 2021·Biophysical Journal·Ada Y ChenAna Damjanovic
Dec 22, 2017·The Journal of Physical Chemistry Letters·Christos M KougentakisBertrand García-Moreno E
Feb 22, 2018·The Journal of Physical Chemistry. B·Aaron C RobinsonBertrand García-Moreno E
Dec 2, 2020·The Journal of Physical Chemistry. B·Ankita Sarkar, Adrian E Roitberg
Oct 13, 2020·The Journal of Physical Chemistry Letters·Amit Kumawat, Suman Chakrabarty

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