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Dissecting electrostatic interactions in Bacillus circulans xylanase through NMR-monitored pH titrations.
MedLine Citation:
PMID:  21947911     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
NMR-monitored pH titration curves of proteins provide a rich source of structural and electrostatic information. Although relatively straightforward to measure, interpreting pH-dependent chemical shift changes to obtain site-specific acid dissociation constants (pK (A) values) is challenging. In order to analyze the biphasic titrations exhibited by the side chain (13)C(γ) nuclei of the nucleophilic Glu78 and general acid/base Glu172 in Bacillus circulans xylanase, we have revisited the formalism for the ionization equilibria of two coupled acidic residues. In general, fitting NMR-monitored pH titration curves for such a system will only yield the two macroscopic pK (A) values that reflect the combined effects of both deprotonation reactions. However, through the use of mutations complemented with ionic strength-dependent measurements, we are able to extract the four microscopic pK (Ai) values governing the branched acid/base equilibria of Glu78 and Glu172 in BcX. These data, confirmed through theoretical calculations, help explain the pH-dependent mechanism of this model GH11 xylanase by demonstrating that the kinetically determined pK (A) values and hence catalytic roles of these two residues result from their electrostatic coupling.
Authors:
Lawrence P McIntosh; Daigo Naito; Simon J Baturin; Mark Okon; Manish D Joshi; Jens E Nielsen
Publication Detail:
Type:  Journal Article     Date:  2011-09-27
Journal Detail:
Title:  Journal of biomolecular NMR     Volume:  51     ISSN:  1573-5001     ISO Abbreviation:  J. Biomol. NMR     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9110829     Medline TA:  J Biomol NMR     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  5-19     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology, Department of Chemistry, and Michael Smith Laboratories, Life Sciences Centre, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada, mcintosh@chem.ubc.ca.
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